Skip to main content
SpringerLink
Log in

Complex Regulation of X-Chromosome Inactivation in Mammals by Long Non-coding RNAs

  • Chapter
  • First Online:
Molecular Biology of Long Non-coding RNAs

Abstract

Organisms in which gender is genetically encoded require a dosage compensation process to equalize sex-linked gene expression between the hetero- and homogametic sexes. In mammals, this dosage compensation process is termed X-chromosome inactivation (XCI). XCI results in the near-complete transcriptional silencing of a single X in XX females, ensuring that only one X per diploid genome remains active. Once stably inactivated, the silent state of the chosen X can be propagated in each cell for the life of the organism, making XCI a paradigm of epigenetic regulation. Since its discovery more than 50 years ago (Lyon, Nature 190:372–373, 1961), significant progress has been made toward understanding XCI. In this chapter, we discuss recent advances in the field, with a focus on XCI in the mouse and the roles that long noncoding RNAs play in regulating the process.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Agrelo, R., Souabni, A., Novatchkova, M., Haslinger, C., Leeb, M., Komnenovic, V., Kishimoto, H., Gresh, L., Kohwi-Shigematsu, T., Kenner, L., et al. (2009). SATB1 defines the developmental context for gene silencing by Xist in lymphoma and embryonic cells. Developmental Cell, 16, 507–516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aguzzi, A., & Altmeyer, M. (2016). Phase separation: Linking cellular compartmentalization to disease. Trends in Cell Biology, 26, 547–558.

    Article  CAS  PubMed  Google Scholar 

  • Almeida, M., Pintacuda, G., Masui, O., Koseki, Y., Gdula, M., Cerase, A., Brown, D., Mould, A., Innocent, C., Nakayama, M., et al. (2017). PCGF3/5-PRC1 initiates Polycomb recruitment in X chromosome inactivation. Science, 356, 1081–1084.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alvarez, J. D., Yasui, D. H., Niida, H., Joh, T., Loh, D. Y., & Kohwi-Shigematsu, T. (2000). The MAR-binding protein SATB1 orchestrates temporal and spatial expression of multiple genes during T-cell development. Genes & Development, 14, 521–535.

    CAS  Google Scholar 

  • Arieti, F., Gabus, C., Tambalo, M., Huet, T., Round, A., & Thore, S. (2014). The crystal structure of the Split end protein SHARP adds a new layer of complexity to proteins containing RNA recognition motifs. Nucleic Acids Research, 42, 6742–6752.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asano, K., Clayton, J., Shalev, A., & Hinnebusch, A. G. (2000). A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(met) is an important translation initiation intermediate in vivo. Genes & Development, 14, 2534–2546.

    Article  CAS  Google Scholar 

  • Augui, S., Filion, G. J., Huart, S., Nora, E., Guggiari, M., Maresca, M., Stewart, A. F., & Heard, E. (2007). Sensing X chromosome pairs before X inactivation via a novel X-pairing region of the Xic. Science, 318, 1632–1636.

    Article  CAS  PubMed  Google Scholar 

  • Bacher, C. P., Guggiari, M., Brors, B., Augui, S., Clerc, P., Avner, P., Eils, R., & Heard, E. (2006). Transient colocalization of X-inactivation centres accompanies the initiation of X inactivation. Nature Cell Biology, 8, 293–299.

    Article  CAS  PubMed  Google Scholar 

  • Barakat, T. S., Gunhanlar, N., Pardo, C. G., Achame, E. M., Ghazvini, M., Boers, R., Kenter, A., Rentmeester, E., Grootegoed, J. A., & Gribnau, J. (2011). RNF12 activates Xist and is essential for X chromosome inactivation. PLoS Genetics, 7, e1002001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barakat, T. S., Loos, F., van Staveren, S., Myronova, E., Ghazvini, M., Grootegoed, J. A., & Gribnau, J. (2014). The trans-activator RNF12 and cis-acting elements effectuate X chromosome inactivation independent of X-pairing. Molecular Cell, 53, 965–978.

    Article  CAS  PubMed  Google Scholar 

  • Beletskii, A., Hong, Y. K., Pehrson, J., Egholm, M., & Strauss, W. M. (2001). PNA interference mapping demonstrates functional domains in the noncoding RNA Xist. Proceedings of the National Academy of Sciences of the United States of America, 98, 9215–9220.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bourdet, A., Ciaudo, C., Zakin, L., Elalouf, J. M., Rusniok, C., Weissenbach, J., & Avner, P. (2006). A SAGE approach to identifying novel trans-acting factors involved in the X inactivation process. Cytogenetic and Genome Research, 113, 325–335.

    Article  CAS  PubMed  Google Scholar 

  • Brockdorff, N. (2011). Chromosome silencing mechanisms in X-chromosome inactivation: Unknown unknowns. Development, 138, 5057–5065.

    Article  CAS  PubMed  Google Scholar 

  • Brockdorff, N., Ashworth, A., Kay, G. F., McCabe, V. M., Norris, D. P., Cooper, P. J., Swift, S., & Rastan, S. (1992). The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell, 71, 515–526.

    Article  CAS  PubMed  Google Scholar 

  • Brown, C. J., Ballabio, A., Rupert, J. L., Lafreniere, R. G., Grompe, M., Tonlorenzi, R., & Willard, H. F. (1991a). A gene from the region of the human X inactivation Centre is expressed exclusively from the inactive X chromosome. Nature, 349, 38–44.

    Article  CAS  PubMed  Google Scholar 

  • Brown, C. J., Lafreniere, R. G., Powers, V. E., Sebastio, G., Ballabio, A., Pettigrew, A. L., Ledbetter, D. H., Levy, E., Craig, I. W., & Willard, H. F. (1991b). Localization of the X inactivation Centre on the human X chromosome in Xq13. Nature, 349, 82–84.

    Article  CAS  PubMed  Google Scholar 

  • Brown, C. J., Hendrich, B. D., Rupert, J. L., Lafreniere, R. G., Xing, Y., Lawrence, J., & Willard, H. F. (1992). The human XIST gene: Analysis of a 17 kb inactive X-specific RNA that contains conserved repeats and is highly localized within the nucleus. Cell, 71, 527–542.

    Article  CAS  PubMed  Google Scholar 

  • Cabili, M. N., Trapnell, C., Goff, L., Koziol, M., Tazon-Vega, B., Regev, A., & Rinn, J. L. (2011). Integrative annotation of human large intergenic noncoding RNAs reveals global properties and specific subclasses. Genes & Development, 25, 1915–1927.

    Article  CAS  Google Scholar 

  • Calabrese, J. M., Sun, W., Song, L., Mugford, J. W., Williams, L., Yee, D., Starmer, J., Mieczkowski, P., Crawford, G. E., & Magnuson, T. (2012). Site-specific silencing of regulatory elements as a mechanism of X inactivation. Cell, 151, 951–963.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cerase, A., Smeets, D., Tang, Y. A., Gdula, M., Kraus, F., Spivakov, M., Moindrot, B., Leleu, M., Tattermusch, A., Demmerle, J., et al. (2014). Spatial separation of Xist RNA and polycomb proteins revealed by superresolution microscopy. Proceedings of the National Academy of Sciences of the United States of America, 111, 2235–2240.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chadwick, B. P., & Willard, H. F. (2004). Multiple spatially distinct types of facultative heterochromatin on the human inactive X chromosome. Proceedings of the National Academy of Sciences of the United States of America, 101, 17450–17455.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chaumeil, J., Le Baccon, P., Wutz, A., & Heard, E. (2006). A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes and Development, 20, 2223–2237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, C. K., Blanco, M., Jackson, C., Aznauryan, E., Ollikainen, N., Surka, C., Chow, A., Cerase, A., McDonel, P., & Guttman, M. (2016). Xist recruits the X chromosome to the nuclear lamina to enable chromosome-wide silencing. Science, 354, 468–472.

    Article  CAS  PubMed  Google Scholar 

  • Chow, J. C., Ciaudo, C., Fazzari, M. J., Mise, N., Servant, N., Glass, J. L., Attreed, M., Avner, P., Wutz, A., Barillot, E., et al. (2010). LINE-1 activity in facultative heterochromatin formation during X chromosome inactivation. Cell, 141, 956–969.

    Article  CAS  PubMed  Google Scholar 

  • Chu, C., Zhang, Q. C., da Rocha, S. T., Flynn, R. A., Bharadwaj, M., Calabrese, J. M., Magnuson, T., Heard, E., & Chang, H. Y. (2015). Systematic discovery of xist RNA binding proteins. Cell, 161, 404–416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chureau, C., Chantalat, S., Romito, A., Galvani, A., Duret, L., Avner, P., & Rougeulle, C. (2011). Ftx is a non-coding RNA which affects Xist expression and chromatin structure within the X-inactivation center region. Human Molecular Genetics, 20, 705–718.

    Article  CAS  PubMed  Google Scholar 

  • Ciaudo, C., Bourdet, A., Cohen-Tannoudji, M., Dietz, H. C., Rougeulle, C., & Avner, P. (2006). Nuclear mRNA degradation pathway(s) are implicated in Xist regulation and X chromosome inactivation. PLoS Genetics, 2, e94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Clemson, C. M., McNeil, J. A., Willard, H. F., & Lawrence, J. B. (1996). XIST RNA paints the inactive X chromosome at interphase: Evidence for a novel RNA involved in nuclear/chromosome structure. The Journal of Cell Biology, 132, 259–275.

    Article  CAS  PubMed  Google Scholar 

  • Clerc, P., & Avner, P. (1998). Role of the region 3′ to Xist exon 6 in the counting process of X-chromosome inactivation. Nature Genetics, 19, 249–253.

    Article  CAS  PubMed  Google Scholar 

  • Cohen, D. E., Davidow, L. S., Erwin, J. A., Xu, N., Warshawsky, D., & Lee, J. T. (2007). The DXPas34 repeat regulates random and imprinted X inactivation. Developmental Cell, 12, 57–71.

    Article  CAS  PubMed  Google Scholar 

  • Cooper, S., Grijzenhout, A., Underwood, E., Ancelin, K., Zhang, T., Nesterova, T. B., Anil-Kirmizitas, B., Bassett, A., Kooistra, S. M., Agger, K., et al. (2016). Jarid2 binds mono-ubiquitylated H2A lysine 119 to mediate crosstalk between Polycomb complexes PRC1 and PRC2. Nature Communications, 7, 13661.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Costanzi, C., & Pehrson, J. R. (1998). Histone macroH2A1 is concentrated in the inactive X chromosome of female mammals. Nature, 393, 599–601.

    Article  CAS  PubMed  Google Scholar 

  • Courtier, B., Heard, E., & Avner, P. (1995). Xce haplotypes show modified methylation in a region of the active X chromosome lying 3′ to Xist. Proceedings of the National Academy of Sciences of the United States of America, 92, 3531–3535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Csankovszki, G., Panning, B., Bates, B., Pehrson, J. R., & Jaenisch, R. (1999). Conditional deletion of Xist disrupts histone macroH2A localization but not maintenance of X inactivation. Nature Genetics, 22, 323–324.

    Article  CAS  PubMed  Google Scholar 

  • da Rocha, S. T., Boeva, V., Escamilla-Del-Arenal, M., Ancelin, K., Granier, C., Matias, N. R., Sanulli, S., Chow, J., Schulz, E., Picard, C., et al. (2014). Jarid2 is implicated in the initial Xist-induced targeting of PRC2 to the inactive X chromosome. Molecular Cell, 53, 301–316.

    Article  PubMed  CAS  Google Scholar 

  • de Belle, I., Cai, S., & Kohwi-Shigematsu, T. (1998). The genomic sequences bound to special AT-rich sequence-binding protein 1 (SATB1) in vivo in Jurkat T cells are tightly associated with the nuclear matrix at the bases of the chromatin loops. The Journal of Cell Biology, 141, 335–348.

    Article  PubMed  PubMed Central  Google Scholar 

  • Debrand, E., Chureau, C., Arnaud, D., Avner, P., & Heard, E. (1999). Functional analysis of the DXPas34 locus, a 3′ regulator of Xist expression. Molecular and Cellular Biology, 19, 8513–8525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Denisenko, O. N., & Bomsztyk, K. (1997). The product of the murine homolog of the Drosophila extra sex combs gene displays transcriptional repressor activity. Molecular and Cellular Biology, 17, 4707–4717.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Derrien, T., Johnson, R., Bussotti, G., Tanzer, A., Djebali, S., Tilgner, H., Guernec, G., Martin, D., Merkel, A., Knowles, D. G., et al. (2012). The GENCODE v7 catalog of human long noncoding RNAs: Analysis of their gene structure, evolution, and expression. Genome Research, 22, 1775–1789.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donohoe, M. E., Zhang, L. F., Xu, N., Shi, Y., & Lee, J. T. (2007). Identification of a Ctcf cofactor, Yy1, for the X chromosome binary switch. Molecular Cell, 25, 43–56.

    Article  CAS  PubMed  Google Scholar 

  • Donohoe, M. E., Silva, S. S., Pinter, S. F., Xu, N., & Lee, J. T. (2009). The pluripotency factor Oct4 interacts with Ctcf and also controls X-chromosome pairing and counting. Nature, 460, 128–132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dunham, I., Kundaje, A., Aldred, S. F., Collins, P. J., Davis, C. A., Doyle, F., Epstein, C. B., Frietze, S., Harrow, J., Kaul, R., et al. (2012). An integrated encyclopedia of DNA elements in the human genome. Nature, 489, 57–74.

    Article  CAS  Google Scholar 

  • Duthie, S. M., Nesterova, T. B., Formstone, E. J., Keohane, A. M., Turner, B. M., Zakian, S. M., & Brockdorff, N. (1999). Xist RNA exhibits a banded localization on the inactive X chromosome and is excluded from autosomal material in cis. Human Molecular Genetics, 8, 195–204.

    Article  CAS  PubMed  Google Scholar 

  • Engelke, R., Riede, J., Hegermann, J., Wuerch, A., Eimer, S., Dengjel, J., & Mittler, G. (2014). The quantitative nuclear matrix proteome as a biochemical snapshot of nuclear organization. Journal of Proteome Research, 13, 3940–3956.

    Article  CAS  PubMed  Google Scholar 

  • Engreitz, J. M., Pandya-Jones, A., McDonel, P., Shishkin, A., Sirokman, K., Surka, C., Kadri, S., Xing, J., Goren, A., Lander, E. S., et al. (2013). The Xist lncRNA exploits three-dimensional genome architecture to spread across the X chromosome. Science, 341, 1237973.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fang, R., Moss, W. N., Rutenberg-Schoenberg, M., & Simon, M. D. (2015). Probing Xist RNA structure in cells using targeted structure-seq. PLoS Genetics, 11, e1005668.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fujita, P. A., Rhead, B., Zweig, A. S., Hinrichs, A. S., Karolchik, D., Cline, M. S., Goldman, M., Barber, G. P., Clawson, H., Coelho, A., et al. (2010). The UCSC genome browser database: Update 2011. Nucleic Acids Research, 39, D876–D882.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Furlan, G., Gutierrez Hernandez, N., Huret, C., Galupa, R., van Bemmel, J. G., Romito, A., Heard, E., Morey, C., & Rougeulle, C. (2018). The Ftx noncoding locus controls X chromosome inactivation independently of its RNA products. Molecular Cell, 70, 462–472 e468.

    Article  CAS  PubMed  Google Scholar 

  • Gayen, S., Maclary, E., Buttigieg, E., Hinten, M., & Kalantry, S. (2015). A primary role for the Tsix lncRNA in maintaining random X-chromosome inactivation. Cell Reports, 11, 1251–1265.

    Article  CAS  PubMed  Google Scholar 

  • Giorgetti, L., Lajoie, B. R., Carter, A. C., Attia, M., Zhan, Y., Xu, J., Chen, C. J., Kaplan, N., Chang, H. Y., Heard, E., et al. (2016). Structural organization of the inactive X chromosome in the mouse. Nature, 535, 575–579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gontan, C., Achame, E. M., Demmers, J., Barakat, T. S., Rentmeester, E., van, I. W., Grootegoed, J. A., & Gribnau, J. (2012). RNF12 initiates X-chromosome inactivation by targeting REX1 for degradation. Nature, 485, 386–390.

    Article  CAS  PubMed  Google Scholar 

  • Grant, J., Mahadevaiah, S. K., Khil, P., Sangrithi, M. N., Royo, H., Duckworth, J., McCarrey, J. R., VandeBerg, J. L., Renfree, M. B., Taylor, W., et al. (2012). Rsx is a metatherian RNA with Xist-like properties in X-chromosome inactivation. Nature, 487, 254–258.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hacisuleyman, E., Goff, L. A., Trapnell, C., Williams, A., Henao-Mejia, J., Sun, L., McClanahan, P., Hendrickson, D. G., Sauvageau, M., Kelley, D. R., et al. (2014). Topological organization of multichromosomal regions by the long intergenic noncoding RNA firre. Nature Structural & Molecular Biology, 21, 198.

    Article  CAS  Google Scholar 

  • Hasegawa, Y., Brockdorff, N., Kawano, S., Tsutui, K., & Nakagawa, S. (2010). The matrix protein hnRNP U is required for chromosomal localization of Xist RNA. Developmental Cell, 19, 469–476.

    Article  CAS  PubMed  Google Scholar 

  • Heard, E., Simmler, M. C., Larin, Z., Rougeulle, C., Courtier, B., Lehrach, H., & Avner, P. (1993). Physical mapping and YAC contig analysis of the region surrounding Xist on the mouse X chromosome. Genomics, 15, 559–569.

    Article  CAS  PubMed  Google Scholar 

  • Heard, E., Mongelard, F., Arnaud, D., & Avner, P. (1999). Xist yeast artificial chromosome transgenes function as X-inactivation centers only in multicopy arrays and not as single copies. Molecular and Cellular Biology, 19, 3156–3166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Helbig, R., & Fackelmayer, F. O. (2003). Scaffold attachment factor a (SAF-A) is concentrated in inactive X chromosome territories through its RGG domain. Chromosoma, 112, 173–182.

    Article  CAS  PubMed  Google Scholar 

  • Hezroni, H., Koppstein, D., Schwartz, M. G., Avrutin, A., Bartel, D. P., & Ulitsky, I. (2015). Principles of long noncoding RNA evolution derived from direct comparison of transcriptomes in 17 species. Cell Reports, 11, 1110–1122.

    Article  CAS  PubMed  Google Scholar 

  • Hoki, Y., Kimura, N., Kanbayashi, M., Amakawa, Y., Ohhata, T., Sasaki, H., & Sado, T. (2009). A proximal conserved repeat in the Xist gene is essential as a genomic element for X-inactivation in mouse. Development, 136, 139–146.

    Article  CAS  PubMed  Google Scholar 

  • Hong, Y. K., Ontiveros, S. D., & Strauss, W. M. (2000). A revision of the human XIST gene organization and structural comparison with mouse Xist. Mammalian Genome, 11, 220–224.

    Article  CAS  PubMed  Google Scholar 

  • Houseley, J., & Tollervey, D. (2009). The many pathways of RNA degradation. Cell, 136, 763–776.

    Article  CAS  PubMed  Google Scholar 

  • Huelga, S. C., Vu, A. Q., Arnold, J. D., Liang, T. Y., Liu, P. P., Yan, B. Y., Donohue, J. P., Shiue, L., Hoon, S., Brenner, S., et al. (2012). Integrative genome-wide analysis reveals cooperative regulation of alternative splicing by hnRNP proteins. Cell Reports, 1, 167–178.

    Article  CAS  PubMed  Google Scholar 

  • Iyer, M. K., Niknafs, Y. S., Malik, R., Singhal, U., Sahu, A., Hosono, Y., Barrette, T. R., Prensner, J. R., Evans, J. R., Zhao, S., et al. (2015). The landscape of long noncoding RNAs in the human transcriptome. Nature Genetics, 47(3), 199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeon, Y., & Lee, J. T. (2011). YY1 tethers Xist RNA to the inactive X nucleation center. Cell, 146, 119–133.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jonkers, I., Monkhorst, K., Rentmeester, E., Grootegoed, J. A., Grosveld, F., & Gribnau, J. (2008). Xist RNA is confined to the nuclear territory of the silenced X chromosome throughout the cell cycle. Molecular and Cellular Biology, 28, 5583–5594.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jonkers, I., Barakat, T. S., Achame, E. M., Monkhorst, K., Kenter, A., Rentmeester, E., Grosveld, F., Grootegoed, J. A., & Gribnau, J. (2009). RNF12 is an X-encoded dose-dependent activator of X chromosome inactivation. Cell, 139, 999–1011.

    Article  CAS  PubMed  Google Scholar 

  • Kalantry, S., Mills, K. C., Yee, D., Otte, A. P., Panning, B., & Magnuson, T. (2006). The Polycomb group protein Eed protects the inactive X-chromosome from differentiation-induced reactivation. Nature Cell Biology, 8, 195–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kalantry, S., Purushothaman, S., Bowen, R. B., Starmer, J., & Magnuson, T. (2009). Evidence of Xist RNA-independent initiation of mouse imprinted X-chromosome inactivation. Nature, 460, 647–651.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kierzek, E., & Kierzek, R. (2003). The thermodynamic stability of RNA duplexes and hairpins containing N6-alkyladenosines and 2-methylthio-N6-alkyladenosines. Nucleic Acids Research, 31, 4472–4480.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, T. K., Hemberg, M., Gray, J. M., Costa, A. M., Bear, D. M., Wu, J., Harmin, D. A., Laptewicz, M., Barbara-Haley, K., Kuersten, S., et al. (2010). Widespread transcription at neuronal activity-regulated enhancers. Nature, 465, 182–187.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kohlmaier, A., Savarese, F., Lachner, M., Martens, J., Jenuwein, T., & Wutz, A. (2004). A chromosomal memory triggered by Xist regulates histone methylation in X inactivation. PLoS Biology, 2, E171.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kopp, F., & Mendell, J. T. (2018). Functional classification and experimental dissection of long noncoding RNAs. Cell, 172, 393–407.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kubota, M., Tran, C., & Spitale, R. C. (2015). Progress and challenges for chemical probing of RNA structure inside living cells. Nature Chemical Biology, 11, 933–941.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lahn, B. T., & Page, D. C. (1999). Four evolutionary strata on the human X chromosome. Science, 286, 964–967.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J. T. (2000). Disruption of imprinted X inactivation by parent-of-origin effects at Tsix. Cell, 103, 17–27.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J. T. (2002). Homozygous Tsix mutant mice reveal a sex-ratio distortion and revert to random X-inactivation. Nature Genetics, 32, 195–200.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J. T. (2005). Regulation of X-chromosome counting by Tsix and Xite sequences. Science, 309, 768–771.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J. T., & Lu, N. (1999). Targeted mutagenesis of Tsix leads to nonrandom X inactivation. Cell, 99, 47–57.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J. T., Strauss, W. M., Dausman, J. A., & Jaenisch, R. (1996). A 450 kb transgene displays properties of the mammalian X-inactivation center. Cell, 86, 83–94.

    Article  CAS  PubMed  Google Scholar 

  • Lee, J. T., Davidow, L. S., & Warshawsky, D. (1999). Tsix, a gene antisense to Xist at the X-inactivation Centre. Nature Genetics, 21, 400–404.

    Article  CAS  PubMed  Google Scholar 

  • Lee, S., Kopp, F., Chang, T. C., Sataluri, A., Chen, B. B., Sivakumar, S., Yu, H. T., Xie, Y., & Mendell, J. T. (2016). Noncoding RNA NORAD regulates genomic stability by sequestering PUMILIO proteins. Cell, 164, 69–80.

    Article  CAS  PubMed  Google Scholar 

  • Li, G., Margueron, R., Ku, M., Chambon, P., Bernstein, B. E., & Reinberg, D. (2010). Jarid2 and PRC2, partners in regulating gene expression. Genes and Development, 24, 368–380.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Liu, N., Dai, Q., Zheng, G. Q., He, C., Parisien, M., & Pan, T. (2015). N-6-methyladenosine-dependent RNA structural switches regulate RNA-protein interactions. Nature, 518, 560–564.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, F., Somarowthu, S., & Pyle, A. M. (2017). Visualizing the secondary and tertiary architectural domains of lncRNA RepA. Nature Chemical Biology, 13, 282–289.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Livernois, A. M., Graves, J. A., & Waters, P. D. (2012). The origin and evolution of vertebrate sex chromosomes and dosage compensation. Heredity, 108, 50–58.

    Article  CAS  PubMed  Google Scholar 

  • Lu, Z. P., Zhang, Q. C., Lee, B., Flynn, R. A., Smith, M. A., Robinson, J. T., Davidovich, C., Gooding, A. R., Goodrich, K. J., Mattick, J. S., et al. (2016). RNA duplex map in living cells reveals higher-order transcriptome structure. Cell, 165, 1267–1279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luikenhuis, S., Wutz, A., & Jaenisch, R. (2001). Antisense transcription through the Xist locus mediates Tsix function in embryonic stem cells. Molecular and Cellular Biology, 21, 8512–8520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lyon, M. F. (1961). Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature, 190, 372–373.

    Article  CAS  PubMed  Google Scholar 

  • Lyon, M. F. (1998). X-chromosome inactivation: A repeat hypothesis. Cytogenetics and Cell Genetics, 80, 133–137.

    Article  CAS  PubMed  Google Scholar 

  • Lyon, M. F., Searle, A. G., & International Committee on Standardized Genetic Nomenclature for Mice. (1989). Genetic variants and strains of the laboratory mouse (2nd ed.). Oxford/New York/Stuttgart: Oxford University Press/G. Fischer.

    Google Scholar 

  • Ma, M., & Strauss, W. M. (2005). Analysis of the Xist RNA isoforms suggests two distinctly different forms of regulation. Mammalian Genome, 16, 391–404.

    Article  CAS  PubMed  Google Scholar 

  • Maclary, E., Hinten, M., Harris, C., Sethuraman, S., Gayen, S., & Kalantry, S. (2017). PRC2 represses transcribed genes on the imprinted inactive X chromosome in mice. Genome Biology, 18, 82.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Mak, W., Baxter, J., Silva, J., Newall, A. E., Otte, A. P., & Brockdorff, N. (2002). Mitotically stable association of polycomb group proteins eed and enx1 with the inactive x chromosome in trophoblast stem cells. Current Biology, 12, 1016–1020.

    Article  CAS  PubMed  Google Scholar 

  • Mak, W., Nesterova, T. B., de Napoles, M., Appanah, R., Yamanaka, S., Otte, A. P., & Brockdorff, N. (2004). Reactivation of the paternal X chromosome in early mouse embryos. Science, 303, 666–669.

    Article  CAS  PubMed  Google Scholar 

  • Marahrens, Y., Panning, B., Dausman, J., Strauss, W., & Jaenisch, R. (1997). Xist-deficient mice are defective in dosage compensation but not spermatogenesis. Genes & Development, 11, 156–166.

    Article  CAS  Google Scholar 

  • Masui, O., Bonnet, I., Le Baccon, P., Brito, I., Pollex, T., Murphy, N., Hupe, P., Barillot, E., Belmont, A. S., & Heard, E. (2011). Live-cell chromosome dynamics and outcome of X chromosome pairing events during ES cell differentiation. Cell, 145, 447–458.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McHugh, C. A., Chen, C. K., Chow, A., Surka, C. F., Tran, C., McDonel, P., Pandya-Jones, A., Blanco, M., Burghard, C., Moradian, A., et al. (2015). The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3. Nature, 521, 232–236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McMahon, A., Fosten, M., & Monk, M. (1983). X-chromosome inactivation mosaicism in the three germ layers and the germ line of the mouse embryo. Journal of Embryology and Experimental Morphology, 74, 207–220.

    CAS  PubMed  Google Scholar 

  • Memili, E., Hong, Y. K., Kim, D. H., Ontiveros, S. D., & Strauss, W. M. (2001). Murine Xist RNA isoforms are different at their 3′ ends: A role for differential polyadenylation. Gene, 266, 131–137.

    Article  CAS  PubMed  Google Scholar 

  • Mikula, M., Bomsztyk, K., Goryca, K., Chojnowski, K., & Ostrowski, J. (2013). Heterogeneous nuclear ribonucleoprotein (HnRNP) K genome-wide binding survey reveals its role in regulating 3′-end RNA processing and transcription termination at the early growth response 1 (EGR1) gene through XRN2 exonuclease. The Journal of Biological Chemistry, 288, 24788–24798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minajigi, A., Froberg, J. E., Wei, C., Sunwoo, H., Kesner, B., Colognori, D., Lessing, D., Payer, B., Boukhali, M., Haas, W., et al. (2015). Chromosomes. A comprehensive Xist interactome reveals cohesin repulsion and an RNA-directed chromosome conformation. Science, 349, aab2276.

    Article  CAS  Google Scholar 

  • Mlynarczyk-Evans, S., Royce-Tolland, M., Alexander, M. K., Andersen, A. A., Kalantry, S., Gribnau, J., & Panning, B. (2006). X chromosomes alternate between two states prior to random X-inactivation. PLoS Biology, 4, e159.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Moindrot, B., & Brockdorff, N. (2016). RNA binding proteins implicated in Xist-mediated chromosome silencing. Seminars in Cell and Developmental Biology, 56, 58–70.

    Article  CAS  PubMed  Google Scholar 

  • Moindrot, B., Cerase, A., Coker, H., Masui, O., Grijzenhout, A., Pintacuda, G., Schermelleh, L., Nesterova, T. B., & Brockdorff, N. (2015). A pooled shRNA screen identifies Rbm15, Spen, and Wtap as factors required for Xist RNA-mediated silencing. Cell Reports, 12, 562–572.

    Article  CAS  PubMed  Google Scholar 

  • Monfort, A., Di Minin, G., Postlmayr, A., Freimann, R., Arieti, F., Thore, S., & Wutz, A. (2015). Identification of spen as a crucial factor for Xist function through forward genetic screening in haploid embryonic stem cells. Cell Reports, 12, 554–561.

    Article  CAS  PubMed  Google Scholar 

  • Monkhorst, K., Jonkers, I., Rentmeester, E., Grosveld, F., & Gribnau, J. (2008). X inactivation counting and choice is a stochastic process: Evidence for involvement of an X-linked activator. Cell, 132, 410–421.

    Article  CAS  PubMed  Google Scholar 

  • Montagutelli, X. (2000). Effect of the genetic background on the phenotype of mouse mutations. Journal of the American Society of Nephrology, 11(Suppl 16), S101–S105.

    PubMed  Google Scholar 

  • Moreira de Mello, J. C., de Araujo, E. S., Stabellini, R., Fraga, A. M., de Souza, J. E., Sumita, D. R., Camargo, A. A., & Pereira, L. V. (2010). Random X inactivation and extensive mosaicism in human placenta revealed by analysis of allele-specific gene expression along the X chromosome. PLoS One, 5, e10947.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Morey, C., Arnaud, D., Avner, P., & Clerc, P. (2001). Tsix-mediated repression of Xist accumulation is not sufficient for normal random X inactivation. Human Molecular Genetics, 10, 1403–1411.

    Article  CAS  PubMed  Google Scholar 

  • Moumen, A., Masterson, P., O’Connor, M. J., & Jackson, S. P. (2005). hnRNP K: An HDM2 target and transcriptional coactivator of p53 in response to DNA damage. Cell, 123, 1065–1078.

    Article  CAS  PubMed  Google Scholar 

  • Mugford, J. W., Starmer, J., Williams, R. L., Jr., Calabrese, J. M., Mieczkowski, P., Yee, D., & Magnuson, T. (2014). Evidence for local regulatory control of escape from imprinted X chromosome inactivation. Genetics, 197(2), 715–723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naganuma, T., Nakagawa, S., Tanigawa, A., Sasaki, Y. F., Goshima, N., & Hirose, T. (2012). Alternative 3′-end processing of long noncoding RNA initiates construction of nuclear paraspeckles. EMBO Journal, 31, 4020–4034.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Namekawa, S. H., Payer, B., Huynh, K. D., Jaenisch, R., & Lee, J. T. (2010). Two-step imprinted X inactivation: Repeat versus genic silencing in the mouse. Molecular and Cellular Biology, 30, 3187–3205.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Navarro, P., Pichard, S., Ciaudo, C., Avner, P., & Rougeulle, C. (2005). Tsix transcription across the Xist gene alters chromatin conformation without affecting Xist transcription: Implications for X-chromosome inactivation. Genes and Development, 19, 1474–1484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Navarro, P., Chambers, I., Karwacki-Neisius, V., Chureau, C., Morey, C., Rougeulle, C., & Avner, P. (2008). Molecular coupling of Xist regulation and pluripotency. Science, 321, 1693–1695.

    Article  CAS  PubMed  Google Scholar 

  • Nesterova, T. B., Slobodyanyuk, S. Y., Elisaphenko, E. A., Shevchenko, A. I., Johnston, C., Pavlova, M. E., Rogozin, I. B., Kolesnikov, N. N., Brockdorff, N., & Zakian, S. M. (2001). Characterization of the genomic Xist locus in rodents reveals conservation of overall gene structure and tandem repeats but rapid evolution of unique sequence. Genome Research, 11, 833–849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nora, E. P., Lajoie, B. R., Schulz, E. G., Giorgetti, L., Okamoto, I., Servant, N., Piolot, T., van Berkum, N. L., Meisig, J., Sedat, J., et al. (2012). Spatial partitioning of the regulatory landscape of the X-inactivation centre. Nature, 485, 381–385.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ogawa, Y., & Lee, J. T. (2003). Xite, X-inactivation intergenic transcription elements that regulate the probability of choice. Molecular Cell, 11, 731–743.

    Article  CAS  PubMed  Google Scholar 

  • Ohhata, T., Hoki, Y., Sasaki, H., & Sado, T. (2006). Tsix-deficient X chromosome does not undergo inactivation in the embryonic lineage in males: Implications for Tsix-independent silencing of Xist. Cytogenetic and Genome Research, 113, 345–349.

    Article  CAS  PubMed  Google Scholar 

  • Ohhata, T., Hoki, Y., Sasaki, H., & Sado, T. (2008). Crucial role of antisense transcription across the Xist promoter in Tsix-mediated Xist chromatin modification. Development, 135, 227–235.

    Article  CAS  PubMed  Google Scholar 

  • Okamoto, I., Otte, A. P., Allis, C. D., Reinberg, D., & Heard, E. (2004). Epigenetic dynamics of imprinted X inactivation during early mouse development. Science, 303, 644–649.

    Article  CAS  PubMed  Google Scholar 

  • Okamoto, I., Arnaud, D., Le Baccon, P., Otte, A. P., Disteche, C. M., Avner, P., & Heard, E. (2005). Evidence for de novo imprinted X-chromosome inactivation independent of meiotic inactivation in mice. Nature, 438, 369–373.

    Article  CAS  PubMed  Google Scholar 

  • Okamoto, I., Patrat, C., Thepot, D., Peynot, N., Fauque, P., Daniel, N., Diabangouaya, P., Wolf, J. P., Renard, J. P., Duranthon, V., et al. (2012). Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development. Nature, 472, 370–374.

    Article  CAS  Google Scholar 

  • Ostareck-Lederer, A., Ostareck, D. H., Cans, C., NEubauer, G., Bomsztyk, K., Superti-Furga, G., & Hentze, M. W. (2002). c-Src-mediated phosphorylation of hnRNP K drives translational activation of specifically silenced mRNAs. Molecular and Cellular Biology, 22, 4535–4543.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ostertag, E. M., & Kazazian, H. H., Jr. (2001). Biology of mammalian L1 retrotransposons. Annual Review of Genetics, 35, 501–538.

    Article  CAS  PubMed  Google Scholar 

  • Panning, B., & Jaenisch, R. (1996). DNA hypomethylation can activate Xist expression and silence X-linked genes. Genes and Development, 10, 1991–2002.

    Article  CAS  PubMed  Google Scholar 

  • Panning, B., Dausman, J., & Jaenisch, R. (1997). X chromosome inactivation is mediated by Xist RNA stabilization. Cell, 90, 907–916.

    Article  CAS  PubMed  Google Scholar 

  • Patil, D. P., Chen, C. K., Pickering, B. F., Chow, A., Jackson, C., Guttman, M., & Jaffrey, S. R. (2016). m(6)A RNA methylation promotes XIST-mediated transcriptional repression. Nature, 537, 369–36+.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patrat, C., Okamoto, I., Diabangouaya, P., Vialon, V., Le Baccon, P., Chow, J., & Heard, E. (2009). Dynamic changes in paternal X-chromosome activity during imprinted X-chromosome inactivation in mice. Proceedings of the National Academy of Sciences of the United States of America, 106, 5198–5203.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Penny, G. D., Kay, G. F., Sheardown, S. A., Rastan, S., & Brockdorff, N. (1996). Requirement for Xist in X chromosome inactivation. Nature, 379, 131–137.

    Article  CAS  PubMed  Google Scholar 

  • Petropoulos, S., Edsgard, D., Reinius, B., Deng, Q. L., Panula, S. P., Codeluppi, S., Reyes, A. P., Linnarsson, S., Sandberg, R., & Lanner, F. (2016). Single-cell RNA-seq reveals lineage and X chromosome dynamics in human preimplantation embryos. Cell, 165, 1012–1026.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pintacuda, G., Wei, G., Roustan, C., Kirmizitas, B. A., Solcan, N., Cerase, A., Castello, A., Mohammed, S., Moindrot, B., Nesterova, T. B., et al. (2017). hnRNPK recruits PCGF3/5-PRC1 to the Xist RNA B-repeat to establish polycomb-mediated chromosomal silencing. Molecular Cell, 68, 955–969 e910.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Plath, K., Fang, J., Mlynarczyk-Evans, S. K., Cao, R., Worringer, K. A., Wang, H., de la Cruz, C. C., Otte, A. P., Panning, B., & Zhang, Y. (2003). Role of histone H3 lysine 27 methylation in X inactivation. Science, 300, 131–135.

    Article  CAS  PubMed  Google Scholar 

  • Popova, B. C., Tada, T., Takagi, N., Brockdorff, N., & Nesterova, T. B. (2006). Attenuated spread of X-inactivation in an X;autosome translocation. Proceedings of the National Academy of Sciences of the United States of America, 103, 7706–7711.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Powell, C. M. (2005). Sex chromosome and sex chromosome abnormalities. In S. Gersen & M. Keagle (Eds.), The principles of clinical cytogenetics, III (pp. 207–246). Totowa: Humana Press.

    Chapter  Google Scholar 

  • Pullirsch, D., Hartel, R., Kishimoto, H., Leeb, M., Steiner, G., & Wutz, A. (2010). The Trithorax group protein Ash2l and Saf-A are recruited to the inactive X chromosome at the onset of stable X inactivation. Development, 137, 935–943.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ramaswami, M., Taylor, J. P., & Parker, R. (2013). Altered ribostasis: RNA-protein granules in degenerative disorders. Cell, 154, 727–736.

    Article  CAS  PubMed  Google Scholar 

  • Rastan, S. (1982). Timing of X-chromosome inactivation in postimplantation mouse embryos. Journal of Embryology and Experimental Morphology, 71, 11–24.

    CAS  PubMed  Google Scholar 

  • Rastan, S. (1994). X chromosome inactivation and the Xist gene. Current Opinion in Genetics and Development, 4, 292–297.

    Article  CAS  PubMed  Google Scholar 

  • Rastan, S., & Brown, S. D. (1990). The search for the mouse X-chromosome inactivation centre. Genetical Research, 56, 99–106.

    Article  CAS  PubMed  Google Scholar 

  • Reyes-Turcu, F. E., & Grewal, S. I. (2012). Different means, same end-heterochromatin formation by RNAi and RNAi-independent RNA processing factors in fission yeast. Current Opinion in Genetics & Development, 22, 156–163.

    Article  CAS  Google Scholar 

  • Rice, G. M., Leonard, C. W., & Weeks, K. M. (2014). RNA secondary structure modeling at consistent high accuracy using differential SHAPE. RNA - A Publication of the RNA Society, 20, 846–854.

    Article  CAS  Google Scholar 

  • Ridings-Figueroa, R., Stewart, E. R., Nesterova, T. B., Coker, H., Pintacuda, G., Godwin, J., Wilson, R., Haslam, A., Lilley, F., Ruigrok, R., et al. (2017). The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory. Genes and Development, 31, 876–888.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Royce-Tolland, M. E., Andersen, A. A., Koyfman, H. R., Talbot, D. J., Wutz, A., Tonks, I. D., Kay, G. F., & Panning, B. (2010). The A-repeat links ASF/SF2-dependent Xist RNA processing with random choice during X inactivation. Nature Structural and Molecular Biology, 17, 948–954.

    Article  CAS  PubMed  Google Scholar 

  • Sado, T., Wang, Z., Sasaki, H., & Li, E. (2001). Regulation of imprinted X-chromosome inactivation in mice by Tsix. Development, 128, 1275–1286.

    CAS  PubMed  Google Scholar 

  • Sado, T., Li, E., & Sasaki, H. (2002). Effect of TSIX disruption on XIST expression in male ES cells. Cytogenetic and Genome Research, 99, 115–118.

    Article  CAS  PubMed  Google Scholar 

  • Sado, T., Hoki, Y., & Sasaki, H. (2005). Tsix silences Xist through modification of chromatin structure. Developmental Cell, 9, 159–165.

    Article  CAS  PubMed  Google Scholar 

  • Sado, T., Hoki, Y., & Sasaki, H. (2006). Tsix defective in splicing is competent to establish Xist silencing. Development, 133, 4925–4931.

    Article  CAS  PubMed  Google Scholar 

  • Sahakyan, A., Kim, R., Chronis, C., Sabri, S., Bonora, G., Theunissen, T. W., Kuoy, E., Langerman, J., Clark, A. T., Jaenisch, R., et al. (2016). Human naive pluripotent stem cells model X chromosome dampening and X inactivation. Cell Stem Cell, 20(1), 87–101.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sakaguchi, T., Hasegawa, Y., Brockdorff, N., Tsutsui, K., Tsutsui, K. M., Sado, T., & Nakagawa, S. (2016). Control of chromosomal localization of Xist by hnRNP U family molecules. Developmental Cell, 39, 11–12.

    Article  CAS  PubMed  Google Scholar 

  • Sarma, K., Levasseur, P., Aristarkhov, A., & Lee, J. T. (2010). Locked nucleic acids (LNAs) reveal sequence requirements and kinetics of Xist RNA localization to the X chromosome. Proceedings of the National Academy of Sciences of the United States of America, 107, 22196–22201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarma, K., Cifuentes-Rojas, C., Ergun, A., del Rosario, A., Jeon, Y., White, F., Sadreyev, R., & Lee, J. T. (2014). ATRX directs binding of PRC2 to Xist RNA and Polycomb targets. Cell, 159, 869–883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Senner, C. E., Nesterova, T. B., Norton, S., Dewchand, H., Godwin, J., Mak, W., & Brockdorff, N. (2011). Disruption of a conserved region of Xist exon 1 impairs Xist RNA localisation and X-linked gene silencing during random and imprinted X chromosome inactivation. Development, 138, 1541–1550.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharman, G. B. (1971). Late DNA replication in the paternally derived X chromosome of female kangaroos. Nature, 230, 231–232.

    Article  CAS  PubMed  Google Scholar 

  • Sheardown, S. A., Duthie, S. M., Johnston, C. M., Newall, A. E., Formstone, E. J., Arkell, R. M., Nesterova, T. B., Alghisi, G. C., Rastan, S., & Brockdorff, N. (1997). Stabilization of Xist RNA mediates initiation of X chromosome inactivation. Cell, 91, 99–107.

    Article  CAS  PubMed  Google Scholar 

  • Shi, Y. H., Downes, M., Xie, W., Kao, H. Y., Ordentlich, P., Tsai, C. C., Hon, M., & Evans, R. M. (2001). Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. Genes and Development, 15, 1140–1151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shin, J., Bossenz, M., Chung, Y., Ma, H., Byron, M., Taniguchi-Ishigaki, N., Zhu, X., Jiao, B., Hall, L. L., Green, M. R., et al. (2010). Maternal Rnf12/RLIM is required for imprinted X-chromosome inactivation in mice. Nature, 467, 977–981.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Silva, J., Mak, W., Zvetkova, I., Appanah, R., Nesterova, T. B., Webster, Z., Peters, A. H., Jenuwein, T., Otte, A. P., & Brockdorff, N. (2003). Establishment of histone h3 methylation on the inactive X chromosome requires transient recruitment of Eed-Enx1 polycomb group complexes. Developmental Cell, 4, 481–495.

    Article  CAS  PubMed  Google Scholar 

  • Smeets, D., Markaki, Y., Schmid, V. J., Kraus, F., Tattermusch, A., Cerase, A., Sterr, M., Fiedler, S., Demmerle, J., Popken, J., et al. (2014). Three-dimensional super-resolution microscopy of the inactive X chromosome territory reveals a collapse of its active nuclear compartment harboring distinct Xist RNA foci. Epigenetics and Chromatin, 7, 8.

    Article  PubMed  PubMed Central  Google Scholar 

  • Smola, M. J., Christy, T. W., Inoue, K., Nicholson, C., Friedersdorf, M., Keene, J., Calabrese, J. M., & Weeks, K. M. (2016). SHAPE reveals transcript-wide interactions, complex structural domains, and principles of protein interaction across the Xist lncRNA in living cells. Proceedings of the National Academy of Sciences of the United States of America, 113, 10322–10327.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Spitale, R. C., Flynn, R. A., Torre, E. A., Kool, E. T., & Chang, H. Y. (2014). RNA structural analysis by evolving SHAPE chemistry. Wiley Interdisciplinary Reviews, 5, 867–881.

    Article  CAS  PubMed  Google Scholar 

  • Spitale, R. C., Flynn, R. A., Zhang, Q. C., Crisalli, P., Lee, B., Jung, J. W., Kuchelmeister, H. Y., Batista, P. J., Torre, E. A., Kool, E. T., et al. (2015). Structural imprints in vivo decode RNA regulatory mechanisms. Nature, 519, 486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Splinter, E., de Wit, E., Nora, E. P., Klous, P., van de Werken, H. J., Zhu, Y., Kaaij, L. J., van Ijcken, W., Gribnau, J., Heard, E., et al. (2011). The inactive X chromosome adopts a unique three-dimensional conformation that is dependent on Xist RNA. Genes and Development, 25(13), 1371–1383.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stavropoulos, N., Rowntree, R. K., & Lee, J. T. (2005). Identification of developmentally specific enhancers for Tsix in the regulation of X chromosome inactivation. Molecular and Cellular Biology, 25, 2757–2769.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sugimoto, M., & Abe, K. (2007). X chromosome reactivation initiates in nascent primordial germ cells in mice. PLoS Genetics, 3, e116.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Sunwoo, H., Wu, J. Y., & Lee, J. T. (2015). The Xist RNA-PRC2 complex at 20-nm resolution reveals a low Xist stoichiometry and suggests a hit-and-run mechanism in mouse cells. Proceedings of the National Academy of Sciences of the United States of America, 112, E4216–E4225.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sunwoo, H., Colognori, D., Froberg, J. E., Jeon, Y., & Lee, J. T. (2017). Repeat E anchors Xist RNA to the inactive X chromosomal compartment through CDKN1A-interacting protein (CIZ1). Proceedings of the National Academy of Sciences of the United States of America, 114, 10654–10659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tada, T., Obata, Y., Tada, M., Goto, Y., Nakatsuji, N., Tan, S., Kono, T., & Takagi, N. (2000). Imprint switching for non-random X-chromosome inactivation during mouse oocyte growth. Development, 127, 3101–3105.

    CAS  PubMed  Google Scholar 

  • Takagi, N., & Sasaki, M. (1975). Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse. Nature, 256, 640–642.

    Article  CAS  PubMed  Google Scholar 

  • Tang, Y. A., Huntley, D., Montana, G., Cerase, A., Nesterova, T. B., & Brockdorff, N. (2010). Efficiency of Xist-mediated silencing on autosomes is linked to chromosomal domain organisation. Epigenetics and Chromatin, 3, 10.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Tattermusch, A., & Brockdorff, N. (2011). A scaffold for X chromosome inactivation. Human Genetics, 130(2), 247–253.

    Article  CAS  PubMed  Google Scholar 

  • Tian, D., Sun, S., & Lee, J. T. (2010). The long noncoding RNA, Jpx, is a molecular switch for X chromosome inactivation. Cell, 143, 390–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tomonaga, T., & Levens, D. (1995). Heterogeneous nuclear ribonucleoprotein K is a DNA-binding transactivator. The Journal of Biological Chemistry, 270, 4875–4881.

    Article  CAS  PubMed  Google Scholar 

  • Tyner, C., Barber, G. P., Casper, J., Clawson, H., Diekhans, M., Eisenhart, C., Fischer, C. M., Gibson, D., Gonzalez, J. N., Guruvadoo, L., et al. (2017). The UCSC Genome Browser database: 2017 update. Nucleic Acids Research, 45, D626–D634.

    CAS  PubMed  Google Scholar 

  • Ulitsky, I., & Bartel, D. P. (2013). lincRNAs: Genomics, evolution, and mechanisms. Cell, 154, 26–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vallot, C., Huret, C., Lesecque, Y., Resch, A., Oudrhiri, N., Bennaceur-Griscelli, A., Duret, L., & Rougeulle, C. (2013). XACT, a long noncoding transcript coating the active X chromosome in human pluripotent cells. Nature Genetics, 45, 239–241.

    Article  CAS  PubMed  Google Scholar 

  • Vallot, C., Ouimette, J. F., Makhlouf, M., Feraud, O., Pontis, J., Come, J., Martinat, C., Bennaceur-Griscelli, A., Lalande, M., & Rougeulle, C. (2015). Erosion of X chromosome inactivation in human pluripotent cells initiates with XACT coating and depends on a specific heterochromatin landscape. Cell Stem Cell, 16, 533–546.

    Article  CAS  PubMed  Google Scholar 

  • Vallot, C., Patrat, C., Collier, A. J., Huret, C., Casanova, M., Liyakat Ali, T. M., Tosolini, M., Frydman, N., Heard, E., Rugg-Gunn, P. J., et al. (2017). XACT noncoding RNA competes with XIST in the control of X chromosome activity during human early development. Cell Stem Cell, 20, 102–111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vigneau, S., Augui, S., Navarro, P., Avner, P., & Clerc, P. (2006). An essential role for the DXPas34 tandem repeat and Tsix transcription in the counting process of X chromosome inactivation. Proceedings of the National Academy of Sciences of the United States of America, 103, 7390–7395.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wake, N., Takagi, N., & Sasaki, M. (1976). Non-random inactivation of X chromosome in the rat yolk sac. Nature, 262, 580–581.

    Article  CAS  PubMed  Google Scholar 

  • Wang, X., Miller, D. C., Clark, A. G., & Antczak, D. F. (2012). Random X inactivation in the mule and horse placenta. Genome Research, 22(10), 1855–1863.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, J. L., Syrett, C. M., Kramer, M. C., Basu, A., Atchison, M. L., & Anguera, M. C. (2016). Unusual maintenance of X chromosome inactivation predisposes female lymphocytes for increased expression from the inactive X. Proceedings of the National Academy of Sciences of the United States of America, 113, E2029–E2038.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Webb, S., de Vries, T. J., & Kaufman, M. H. (1992). The differential staining pattern of the X chromosome in the embryonic and extraembryonic tissues of postimplantation homozygous tetraploid mouse embryos. Genetical Research, 59, 205–214.

    Article  CAS  PubMed  Google Scholar 

  • Weintraub, A. S., Li, C. H., Zamudio, A. V., Sigova, A. A., Hannett, N. M., Day, D. S., Abraham, B. J., Cohen, M. A., Nabet, B., Buckley, D. L., et al. (2017). YY1 is a structural regulator of enhancer-promoter loops. Cell, 171, 1573–1588 e1528.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • West, J. D., Frels, W. I., Chapman, V. M., & Papaioannou, V. E. (1977). Preferential expression of the maternally derived X chromosome in the mouse yolk sac. Cell, 12, 873–882.

    Article  CAS  PubMed  Google Scholar 

  • Williams, L. H., Kalantry, S., Starmer, J., & Magnuson, T. (2011). Transcription precedes loss of Xist coating and depletion of H3K27me3 during X-chromosome reprogramming in the mouse inner cell mass. Development, 138, 2049–2057.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wutz, A., & Jaenisch, R. (2000). A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Molecular Cell, 5, 695–705.

    Article  CAS  PubMed  Google Scholar 

  • Wutz, A., Rasmussen, T. P., & Jaenisch, R. (2002). Chromosomal silencing and localization are mediated by different domains of Xist RNA. Nature Genetics, 30, 167–174.

    Article  CAS  PubMed  Google Scholar 

  • Xu, N., Tsai, C. L., & Lee, J. T. (2006). Transient homologous chromosome pairing marks the onset of X inactivation. Science, 311, 1149–1152.

    Article  CAS  PubMed  Google Scholar 

  • Xu, N., Donohoe, M. E., Silva, S. S., & Lee, J. T. (2007). Evidence that homologous X-chromosome pairing requires transcription and Ctcf protein. Nature Genetics, 39, 1390–1396.

    Article  CAS  PubMed  Google Scholar 

  • Xue, F., Tian, X. C., Du, F., Kubota, C., Taneja, M., Dinnyes, A., Dai, Y., Levine, H., Pereira, L. V., & Yang, X. (2002). Aberrant patterns of X chromosome inactivation in bovine clones. Nature Genetics, 31, 216–220.

    Article  CAS  PubMed  Google Scholar 

  • Yamada, N., Hasegawa, Y., Yue, M., Hamada, T., Nakagawa, S., & Ogawa, Y. (2015). Xist exon 7 contributes to the stable localization of Xist RNA on the inactive X-chromosome. PLoS Genetics, 11, e1005430.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Yang, L., Kirby, J. E., Sunwoo, H., & Lee, J. T. (2016). Female mice lacking Xist RNA show partial dosage compensation and survive to term. Genes and Development, 30, 1747–1760.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • You, S. H., Lim, H. W., Sun, Z., Broache, M., Won, K. J., & Lazar, M. A. (2013). Nuclear receptor co-repressors are required for the histone-deacetylase activity of HDAC3 in vivo. Nature Structural and Molecular Biology, 20, 182–187.

    Article  CAS  PubMed  Google Scholar 

  • Zhao, J., Sun, B. K., Erwin, J. A., Song, J. J., & Lee, J. T. (2008). Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science, 322, 750–756.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, USA

    J. Mauro Calabrese

Authors
  1. J. Mauro Calabrese
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to J. Mauro Calabrese .

Editor information

Editors and Affiliations

  1. Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Ahmad M. Khalil

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Calabrese, J.M. (2019). Complex Regulation of X-Chromosome Inactivation in Mammals by Long Non-coding RNAs. In: Khalil, A. (eds) Molecular Biology of Long Non-coding RNAs. Springer, Cham. https://doi.org/10.1007/978-3-030-17086-8_1

Download citation

Publish with us

Policies and ethics

Search

Navigation