Skip to main content
SpringerLink
Log in

Runx1 Structure and Function in Blood Cell Development

  • Chapter
  • First Online:
Book cover RUNX Proteins in Development and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 962))

Abstract

RUNX transcription factors belong to a highly conserved class of transcriptional regulators which play various roles in the development of the majority of metazoans. In this review we focus on the founding member of the family, RUNX1, and its role in the transcriptional control of blood cell development in mammals. We summarize data showing that RUNX1 functions both as activator and repressor within a chromatin environment, a feature that requires its interaction with multiple other transcription factors and co-factors. Furthermore, we outline how RUNX1 works together with other factors to reshape the epigenetic landscape and the three-dimensional structure of gene loci within the nucleus. Finally, we review how aberrant forms of RUNX1 deregulate blood cell development and cause hematopoietic malignancies.

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 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

  • Aikawa, Y., Nguyen, L. A., Isono, K., Takakura, N., Tagata, Y., Schmitz, M. L., et al. (2006). Roles of HIPK1 and HIPK2 in AML1- and p300-dependent transcription, hematopoiesis and blood vessel formation. The EMBO Journal, 25, 3955–3965.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Aziz-Aloya, R. B., Levanon, D., Karn, H., Kidron, D., Goldenberg, D., Lotem, J., et al. (1998). Expression of AML1-d, a short human AML1 isoform, in embryonic stem cells suppresses in vivo tumor growth and differentiation. Cell Death and Differentiation, 5, 765–773.

    Article  CAS  PubMed  Google Scholar 

  • Bae, S. C., Yamaguchi-Iwai, Y., Ogawa, E., Maruyama, M., Inuzuka, M., Kagoshima, H., et al. (1993). Isolation of PEBP2 alpha B cDNA representing the mouse homolog of human acute myeloid leukemia gene, AML1. Oncogene, 8, 809–814.

    CAS  PubMed  Google Scholar 

  • Bae, S. C., Takahashi, E., Zhang, Y. W., Ogawa, E., Shigesada, K., Namba, Y., et al. (1995). Cloning, mapping and expression of PEBP2 alpha C, a third gene encoding the mammalian Runt domain. Gene, 159, 245–248.

    Article  CAS  PubMed  Google Scholar 

  • Bakshi, R., Zaidi, S. K., Pande, S., Hassan, M. Q., Young, D. W., Montecino, M., et al. (2008). The leukemogenic t(8;21) fusion protein AML1-ETO controls rRNA genes and associates with nucleolar-organizing regions at mitotic chromosomes. Journal of Cell Science, 121, 3981–3990.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bakshi, R., Hassan, M. Q., Pratap, J., Lian, J. B., Montecino, M. A., van Wijnen, A. J., et al. (2010). The human SWI/SNF complex associates with RUNX1 to control transcription of hematopoietic target genes. Journal of Cellular Physiology, 225, 569–576.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barnett, D. H., Sheng, S., Charn, T. H., Waheed, A., Sly, W. S., Lin, C. Y., et al. (2008). Estrogen receptor regulation of carbonic anhydrase XII through a distal enhancer in breast cancer. Cancer Research, 68, 3505–3515.

    Article  CAS  PubMed  Google Scholar 

  • Bee, T., Liddiard, K., Swiers, G., Bickley, S. R. B., Vink, C. S., Jarratt, A., et al. (2009). Alternative Runx1 promoter usage in mouse developmental hematopoiesis. Blood Cells, Molecules, and Diseases, 43, 35–42.

    Article  CAS  PubMed  Google Scholar 

  • Ben-Ami, O., Friedman, D., Leshkowitz, D., Goldenberg, D., Orlovsky, K., Pencovich, N., et al. (2013). Addiction of t(8;21) and inv(16) acute myeloid leukemia to native RUNX1. Cell Reports, 4, 1131–1143.

    Article  CAS  PubMed  Google Scholar 

  • Biggs, J. R., Zhang, Y., Peterson, L. F., Garcia, M., Zhang, D. E., & Kraft, A. S. (2005). Phosphorylation of AML1/RUNX1 regulates its degradation and nuclear matrix association. Molecular Cancer Research : MCR, 3, 391–401.

    Article  CAS  PubMed  Google Scholar 

  • Biggs, J. R., Peterson, L. F., Zhang, Y., Kraft, A. S., & Zhang, D. E. (2006). AML1/RUNX1 phosphorylation by cyclin-dependent kinases regulates the degradation of AML1/RUNX1 by the anaphase-promoting complex. Molecular and Cellular Biology, 26, 7420–7429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boney-Montoya, J., Ziegler, Y. S., Curtis, C. D., Montoya, J. A., & Nardulli, A. M. (2010). Long-range transcriptional control of progesterone receptor gene expression. Molecular Endocrinology (Baltimore, MD), 24, 346–358.

    Article  CAS  Google Scholar 

  • Bowers, S. R., Calero-Nieto, F. J., Valeaux, S., Fernandez-Fuentes, N., & Cockerill, P. N. (2010). Runx1 binds as a dimeric complex to overlapping Runx1 sites within a palindromic element in the human GM-CSF enhancer. Nucleic Acids Research, 38, 6124–6134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bristow, C. A. P., & Shore, P. (2003). Transcriptional regulation of the human MIP-1alpha promoter by RUNX1 and MOZ. Nucleic Acids Research, 31, 2735–2744.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brown, R. C., Pattison, S., van Ree, J., Coghill, E., Perkins, A., Jane, S. M., & Cunningham, J. M. (2002). Distinct domains of erythroid Kruppel-like factor modulate chromatin remodeling and transactivation at the endogenous beta-globin gene promoter. Molecular and Cellular Biology, 22, 161–170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carter, D., Chakalova, L., Osborne, C. S., Dai, Y. F., & Fraser, P. (2002). Long-range chromatin regulatory interactions in vivo. Nature Genetics, 32, 623–626.

    Article  CAS  PubMed  Google Scholar 

  • Challen, G. A., & Goodell, M. A. (2010). Runx1 isoforms show differential expression patterns during hematopoietic development but have similar functional effects in adult hematopoietic stem cells. Experimental Hematology, 38, 403–416.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chavanas, S., Adoue, V., Mechin, M. C., Ying, S., Dong, S., Duplan, H., et al. (2008). Long-range enhancer associated with chromatin looping allows AP-1 regulation of the peptidylarginine deiminase 3 gene in differentiated keratinocyte. PloS One, 3, e3408.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen, X., Reitman, M., & Bieker, J. J. (1998). Chromatin structure and transcriptional control elements of the erythroid Kruppel-like factor (EKLF) gene. The Journal of Biological Chemistry, 273, 25031–25040.

    Article  CAS  PubMed  Google Scholar 

  • Chen, M. J., Yokomizo, T., Zeigler, B. M., Dzierzak, E. A., & Speck, N. A. (2009). Runx1 is required for the endothelial to haematopoietic cell transition but not thereafter. Nature, 457, 887–891.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coffman, J. A. (2003). Runx transcription factors and the developmental balance between cell proliferation and differentiation. Cell Biology International, 27, 315–324.

    Article  CAS  PubMed  Google Scholar 

  • Collins, A., Littman, D. R., & Taniuchi, I. (2009). RUNX proteins in transcription factor networks that regulate T-cell lineage choice. Nature Reviews Immunology, 9, 106–115.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Collins, A., Hewitt, S. L., Chaumeil, J., Sellars, M., Micsinai, M., Allinne, J., et al. (2011). RUNX transcription factor-mediated association of Cd4 and Cd8 enables coordinate gene regulation. Immunity, 34, 303–314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dekker, J., & Heard, E. (2015). Structural and functional diversity of Topologically Associating Domains. FEBS Letters, 589, 2877–2884.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deshane, J., Kim, J., Bolisetty, S., Hock, T. D., Hill-Kapturczak, N., & Agarwal, A. (2010). Sp1 regulates chromatin looping between an intronic enhancer and distal promoter of the human heme oxygenase-1 gene in renal cells. The Journal of Biological Chemistry, 285, 16476–16486.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dowdy, C. R., Xie, R., Frederick, D., Hussain, S., Zaidi, S. K., Vradii, D., et al. (2010). Definitive hematopoiesis requires Runx1 C-terminal-mediated subnuclear targeting and transactivation. Human Molecular Genetics, 19, 1048–1057.

    Article  CAS  PubMed  Google Scholar 

  • Draper, J. E., Sroczynska, P., Tsoulaki, O., Leong, H. S., Fadlullah, M. Z. H., Miller, C., et al. (2016). RUNX1B expression is highly heterogeneous and distinguishes megakaryocytic and erythroid lineage fate in adult mouse hematopoiesis. PLoS Genetics, 12, e1005814.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ducy, P., Zhang, R., Geoffroy, V., Ridall, A. L., & Karsenty, G. (1997). Osf2/Cbfa1: A transcriptional activator of osteoblast differentiation. Cell, 89, 747–754.

    Article  CAS  PubMed  Google Scholar 

  • Durst, K. L., & Hiebert, S. W. (2004). Role of RUNX family members in transcriptional repression and gene silencing. Oncogene, 23, 4220–4224.

    Article  CAS  PubMed  Google Scholar 

  • Ebralidze, A. K., Guibal, F. C., Steidl, U., Zhang, P., Lee, S., Bartholdy, B., et al. (2008). PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element. Genes & Development, 22, 2085–2092.

    Article  CAS  Google Scholar 

  • Fujita, Y., Nishimura, M., Taniwaki, M., Abe, T., & Okuda, T. (2001). Identification of an alternatively spliced form of the mouse AML1/RUNX1 gene transcript AML1c and its expression in early hematopoietic development. Biochemical and Biophysical Research Communications, 281, 1248–1255.

    Article  CAS  PubMed  Google Scholar 

  • Fukushima-Nakase, Y., Naoe, Y., Taniuchi, I., Hosoi, H., Sugimoto, T., & Okuda, T. (2005). Shared and distinct roles mediated through C-terminal subdomains of acute myeloid leukemia/Runt-related transcription factor molecules in murine development. Blood, 105, 4298–4307.

    Article  CAS  PubMed  Google Scholar 

  • Goode, D. K., Obier, N., Vijayabaskar, M. S., Lie-a-Ling, M., Lilly, A. J., Hannah, R., et al. (2016). Dynamic gene regulatory networks drive hematopoietic specification and differentiation. Developmental Cell, 36, 572–587.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goyama, S., Yamaguchi, Y., Imai, Y., Kawazu, M., Nakagawa, M., Asai, T., et al. (2004). The transcriptionally active form of AML1 is required for hematopoietic rescue of the AML1-deficient embryonic para-aortic splanchnopleural (P-Sp) region. Blood, 104, 3558–3564.

    Article  CAS  PubMed  Google Scholar 

  • Goyama, S., Schibler, J., Cunningham, L., Zhang, Y., Rao, Y., Nishimoto, N., et al. (2013). Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. The Journal of Clinical Investigation, 123, 3876–3888.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goyama, S., Schibler, J., Gasilina, A., Shrestha, M., Lin, S., Link, K. A., et al. (2016). UBASH3B/Sts-1-CBL axis regulates myeloid proliferation in human preleukemia induced by AML1-ETO. Leukemia, 30, 728–739.

    Article  CAS  PubMed  Google Scholar 

  • Growney, J. D., Shigematsu, H., Li, Z., Lee, B. H., Adelsperger, J., Rowan, R., et al. (2005). Loss of Runx1 perturbs adult hematopoiesis and is associated with a myeloproliferative phenotype. Blood, 106, 494–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gu, T. L., Goetz, T. L., Graves, B. J., & Speck, N. A. (2000). Auto-inhibition and partner proteins, core-binding factor beta (CBFbeta) and Ets-1, modulate DNA binding by CBFalpha2 (AML1). Molecular and Cellular Biology, 20, 91–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo, H., & Friedman, A. D. (2011). Phosphorylation of RUNX1 by cyclin-dependent kinase reduces direct interaction with HDAC1 and HDAC3. Journal of Biological Chemistry, 286, 208–215.

    Article  CAS  PubMed  Google Scholar 

  • Gutierrez, J., Sierra, J., Medina, R., Puchi, M., Imschenetzky, M., van Wijnen, A., et al. (2000). Interaction of CBF alpha/AML/PEBP2 alpha transcription factors with nucleosomes containing promoter sequences requires flexibility in the translational positioning of the histone octamer and exposure of the CBF alpha site. Biochemistry, 39, 13565–13574.

    Article  CAS  PubMed  Google Scholar 

  • Harrington, K. S., Javed, A., Drissi, H., McNeil, S., Lian, J. B., Stein, J. L., et al. (2002). Transcription factors RUNX1/AML1 and RUNX2/Cbfa1 dynamically associate with stationary subnuclear domains. Journal of Cell Science, 115, 4167–4176.

    Article  CAS  PubMed  Google Scholar 

  • Herglotz, J., Kuvardina, O. N., Kolodziej, S., Kumar, A., Hussong, H., Grez, M., & Lausen, J. (2013). Histone arginine methylation keeps RUNX1 target genes in an intermediate state. Oncogene, 32, 2565–2575.

    Article  CAS  PubMed  Google Scholar 

  • Hernandez-Munain, C., Roberts, J. L., & Krangel, M. S. (1998). Cooperation among multiple transcription factors is required for access to minimal T-cell receptor alpha-enhancer chromatin in vivo. Molecular and Cellular Biology, 18, 3223–3233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hoogenkamp, M., Lichtinger, M., Krysinska, H., Lancrin, C., Clarke, D., Williamson, A., et al. (2009). Early chromatin unfolding by RUNX1: A molecular explanation for differential requirements during specification versus maintenance of the hematopoietic gene expression program. Blood, 114, 299–309.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang, G., Shigesada, K., Ito, K., Wee, H.-J., Yokomizo, T., & Ito, Y. (2001). Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation. The EMBO Journal, 20, 723–733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang, G., Zhang, P., Hirai, H., Elf, S., Yan, X., Chen, Z., et al. (2008). PU.1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nature Genetics, 40, 51–60.

    Article  CAS  PubMed  Google Scholar 

  • Huang, G., Zhao, X., Wang, L., Elf, S., Xu, H., Zhao, X., et al. (2011). The ability of MLL to bind RUNX1 and methylate H3K4 at PU.1 regulatory regions is impaired by MDS/AML-associated RUNX1/AML1 mutations. Blood, 118, 6544–6552.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ichikawa, M., Asai, T., Saito, T., Seo, S., Yamazaki, I., Yamagata, T., et al. (2004). AML-1 is required for megakaryocytic maturation and lymphocytic differentiation, but not for maintenance of hematopoietic stem cells in adult hematopoiesis. Nature Medicine, 10, 299–304.

    Article  CAS  PubMed  Google Scholar 

  • Imai, Y., Kurokawa, M., Yamaguchi, Y., Izutsu, K., Nitta, E., Mitani, K., et al. (2004). The corepressor mSin3A regulates phosphorylation-induced activation, intranuclear location, and stability of AML1. Molecular and Cellular Biology, 24, 1033–1043.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inoue, K.-I., Ozaki, S., Shiga, T., Ito, K., Masuda, T., Okado, N., et al. (2002). Runx3 controls the axonal projection of proprioceptive dorsal root ganglion neurons. Nature Neuroscience, 5, 946–954.

    Article  CAS  PubMed  Google Scholar 

  • Jackson, D. A., Hassan, A. B., Errington, R. J., & Cook, P. R. (1993). Visualization of focal sites of transcription within human nuclei. The EMBO Journal, 12, 1059–1065.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Javed, A., Guo, B., Hiebert, S., Choi, J. Y., Green, J., Zhao, S. C., et al. (2000). Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/PEBP2(alpha)) dependent activation of tissue-specific gene transcription. Journal of Cell Science, 113(Pt 12), 2221–2231.

    CAS  PubMed  Google Scholar 

  • Kim, W. Y., Sieweke, M., Ogawa, E., Wee, H.-J., Englmeier, U., Graf, T., et al. (1999). Mutual activation of Ets-1 and AML1 DNA binding by direct interaction of their autoinhibitory domains. The EMBO Journal, 18, 1609–1620.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, S. I., Bultman, S. J., Jing, H., Blobel, G. A., & Bresnick, E. H. (2007). Dissecting molecular steps in chromatin domain activation during hematopoietic differentiation. Molecular and Cellular Biology, 27, 4551–4565.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, S. I., Bultman, S. J., Kiefer, C. M., Dean, A., & Bresnick, E. H. (2009). BRG1 requirement for long-range interaction of a locus control region with a downstream promoter. Proceedings of the National Academy of Sciences of the United States of America, 106, 2259–2264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kindle, K. B., Troke, P. J. F., Collins, H. M., Matsuda, S., Bossi, D., Bellodi, C., et al. (2005). MOZ-TIF2 inhibits transcription by nuclear receptors and p53 by impairment of CBP function. Molecular and Cellular Biology, 25, 988–1002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitabayashi, I. (1998). Interaction and functional cooperation of the leukemia-associated factors AML1 and p300 in myeloid cell differentiation. The EMBO Journal, 17, 2994–3004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kitabayashi, I., Aikawa, Y., Nguyen, L. A., Yokoyama, A., & Ohki, M. (2001). Activation of AML1-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. The EMBO Journal, 20, 7184–7196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Komori, T., Yagi, H., Nomura, S., Yamaguchi, A., Sasaki, K., Deguchi, K., et al. (1997). Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell, 89, 755–764.

    Article  CAS  PubMed  Google Scholar 

  • Kuvardina, O. N., Herglotz, J., Kolodziej, S., Kohrs, N., Herkt, S., Wojcik, B., et al. (2015). RUNX1 represses the erythroid gene expression program during megakaryocytic differentiation. Blood, 125, 3570–3579.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lacaud, G., Gore, L., Kennedy, M., Kouskoff, V., Kingsley, P., Hogan, C., et al. (2002). Runx1 is essential for hematopoietic commitment at the hemangioblast stage of development in vitro. Blood, 100, 458–466.

    Article  CAS  PubMed  Google Scholar 

  • Lam, K., & Zhang, D. E. (2012). RUNX1 and RUNX1-ETO: Roles in hematopoiesis and leukemogenesis. Frontiers in Bioscience, 17, 1120–1139.

    Article  CAS  Google Scholar 

  • Lam, E. Y. N., Chau, J. Y. M., Kalev-Zylinska, M. L., Fountaine, T. M., Mead, R. S., Hall, C. J., et al. (2009). Zebrafish runx1 promoter-EGFP transgenics mark discrete sites of definitive blood progenitors. Blood, 113, 1241–1249.

    Article  CAS  PubMed  Google Scholar 

  • Lancrin, C., Sroczynska, P., Stephenson, C., Allen, T., Kouskoff, V., & Lacaud, G. (2009). The haemangioblast generates haematopoietic cells through a haemogenic endothelium stage. Nature, 457, 892–895.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Leong, W. Y., Guo, H., Ma, O., Huang, H., Cantor, A. B., & Friedman, A. D. (2016). Runx1 phosphorylation by Src increases trans-activation via augmented stability, reduced histone deacetylase (HDAC) binding, and increased dna affinity, and activated Runx1 favors granulopoiesis. The Journal of Biological Chemistry, 291, 826–836.

    Article  CAS  PubMed  Google Scholar 

  • Levanon, D., & Groner, Y. (2004). Structure and regulated expression of mammalian RUNX genes. Oncogene, 23, 4211–4219.

    Article  CAS  PubMed  Google Scholar 

  • Levanon, D., Bernstein, Y., Negreanu, V., Ghozi, M. C., Bar-Am, I., Aloya, R., et al. (1996). A large variety of alternatively spliced and differentially expressed mRNAs are encoded by the human acute myeloid leukemia gene AML1. DNA and Cell Biology, 15, 175–185.

    Article  CAS  PubMed  Google Scholar 

  • Levanon, D., Goldstein, R. E., Bernstein, Y., Tang, H., Goldenberg, D., Stifani, S., et al. (1998). Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors. Proceedings of the National Academy of Sciences of the United States of America, 95, 11590–11595.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levanon, D., Bettoun, D., Harris-Cerruti, C., Woolf, E., Negreanu, V., Eilam, R., et al. (2002). The Runx3 transcription factor regulates development and survival of TrkC dorsal root ganglia neurons. The EMBO Journal, 21, 3454–3463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Levantini, E., Lee, S., Radomska, H. S., Hetherington, C. J., Alberich-Jorda, M., Amabile, G., et al. (2011). RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating interactions with a distal regulatory element. The EMBO Journal, 30, 4059–4070.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lichtinger, M., Ingram, R., Hannah, R., Muller, D., Clarke, D., Assi, S.A., Lie-A-Ling, M., Noailles, L., Vijayabaskar, M.S., Wu, M., et al. (2012). RUNX1 reshapes the epigenetic landscape at the onset of haematopoiesis. The EMBO Journal, 31, 4318–4333.

    Google Scholar 

  • Lie-A-Ling, M., Marinopoulou, E., Li, Y., Patel, R., Stefanska, M., Bonifer, C., et al. (2014). RUNX1 positively regulates a cell adhesion and migration program in murine hemogenic endothelium prior to blood emergence. Blood, 124, e11–e20.

    Article  CAS  PubMed  Google Scholar 

  • Ling, J. Q., Li, T., Hu, J. F., Vu, T. H., Chen, H. L., Qiu, X. W., et al. (2006). CTCF mediates interchromosomal colocalization between Igf2/H19 and Wsb1/Nf1. Science, 312, 269–272.

    Article  CAS  PubMed  Google Scholar 

  • Liu, Y., Chen, W., Gaudet, J., Cheney, M. D., Roudaia, L., Cierpicki, T., et al. (2007). Structural basis for recognition of SMRT/N-CoR by the MYND domain and its contribution to AML1/ETO’s activity. Cancer Cell, 11, 483–497.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu, X., Zhang, Q., Zhang, D. E., Zhou, C., Xing, H., Tian, Z., et al. (2009a). Overexpression of an isoform of AML1 in acute leukemia and its potential role in leukemogenesis. Leukemia, 23, 739–745.

    Article  CAS  PubMed  Google Scholar 

  • Liu, Z., Ma, Z., Terada, L. S., & Garrard, W. T. (2009b). Divergent roles of RelA and c-Rel in establishing chromosomal loops upon activation of the Igkappa gene. Journal of Immunology, 183, 3819–3830.

    Article  CAS  Google Scholar 

  • Lopez-Camacho, C., van Wijnen, A. J., Lian, J. B., Stein, J. L., & Stein, G. S. (2014). CBFbeta and the leukemogenic fusion protein CBFbeta-SMMHC associate with mitotic chromosomes to epigenetically regulate ribosomal genes. Journal of Cellular Biochemistry, 115, 2155–2164.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lutterbach, B., Westendorf, J. J., Linggi, B., Isaac, S., Seto, E., & Hiebert, S. W. (2000). A mechanism of repression by acute myeloid leukemia-1, the target of multiple chromosomal translocations in acute leukemia. The Journal of Biological Chemistry, 275, 651–656.

    Article  CAS  PubMed  Google Scholar 

  • Marenduzzo, D., Faro-Trindade, I., & Cook, P. R. (2007). What are the molecular ties that maintain genomic loops? Trends in Genetics, 23, 126–133.

    Article  CAS  PubMed  Google Scholar 

  • Martens, J. H., Mandoli, A., Simmer, F., Wierenga, B. J., Saeed, S., Singh, A. A., et al. (2012). ERG and FLI1 binding sites demarcate targets for aberrant epigenetic regulation by AML1-ETO in acute myeloid leukemia. Blood, 120, 4038–4048.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matheny, C. J., Speck, M. E., Cushing, P. R., Zhou, Y., Corpora, T., Regan, M., et al. (2007). Disease mutations in RUNX1 and RUNX2 create nonfunctional, dominant-negative, or hypomorphic alleles. The EMBO Journal, 26, 1163–1175.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meier, N., Krpic, S., Rodriguez, P., Strouboulis, J., Monti, M., Krijgsveld, J., et al. (2006). Novel binding partners of Ldb1 are required for haematopoietic development. Development (Cambridge, England), 133, 4913–4923.

    Article  CAS  Google Scholar 

  • Michaud, J., Wu, F., Osato, M., Cottles, G. M., Yanagida, M., Asou, N., et al. (2002). In vitro analyses of known and novel RUNX1/AML1 mutations in dominant familial platelet disorder with predisposition to acute myelogenous leukemia: Implications for mechanisms of pathogenesis. Blood, 99, 1364–1372.

    Article  CAS  PubMed  Google Scholar 

  • Miyoshi, H., Shimizu, K., Kozu, T., Maseki, N., Kaneko, Y., & Ohki, M. (1991). t(8;21) breakpoints on chromosome 21 in acute myeloid leukemia are clustered within a limited region of a single gene, AML1. Proceedings of the National Academy of Sciences of the United States of America, 88, 10431–10434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Miyoshi, H., Ohira, M., Shimizu, K., Mitani, K., Hirai, H., Imai, T., et al. (1995). Alternative splicing and genomic structure of the AML1 gene involved in acute myeloid leukemia. Nucleic Acids Research, 23, 2762–2769.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nutt, S. L., Heavey, B., Rolink, A. G., & Busslinger, M. (1999). Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature, 401, 556–562.

    Article  CAS  PubMed  Google Scholar 

  • Okuda, T., van Deursen, J., Hiebert, S. W., Grosveld, G., & Downing, J. R. (1996). AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell, 84, 321–330.

    Article  CAS  PubMed  Google Scholar 

  • Okumura, A. J., Peterson, L. F., Okumura, F., Boyapati, A., & Zhang, D. E. (2008). t(8;21)(q22;q22) Fusion proteins preferentially bind to duplicated AML1/RUNX1 DNA-binding sequences to differentially regulate gene expression. Blood, 112, 1392–1401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ono, M., Yaguchi, H., Ohkura, N., Kitabayashi, I., Nagamura, Y., Nomura, T., et al. (2007). Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature, 446, 685–689.

    Article  CAS  PubMed  Google Scholar 

  • Osato, M. (2004). Point mutations in the RUNX1/AML1 gene: Another actor in RUNX leukemia. Oncogene, 23, 4284–4296.

    Article  CAS  PubMed  Google Scholar 

  • Osborne, C. S., Chakalova, L., Brown, K. E., Carter, D., Horton, A., Debrand, E., et al. (2004). Active genes dynamically colocalize to shared sites of ongoing transcription. Nature Genetics, 36, 1065–1071.

    Article  CAS  PubMed  Google Scholar 

  • Otto, F., Thornell, A. P., Crompton, T., Denzel, A., Gilmour, K. C., Rosewell, I. R., et al. (1997). Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. Cell, 89, 765–771.

    Article  CAS  PubMed  Google Scholar 

  • Pande, S., Ali, S. A., Dowdy, C., Zaidi, S. K., Ito, K., Ito, Y., et al. (2009). Subnuclear targeting of the Runx3 tumor suppressor and its epigenetic association with mitotic chromosomes. Journal of Cellular Physiology, 218, 473–479.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patrinos, G. P., de Krom, M., de Boer, E., Langeveld, A., Imam, A. M., Strouboulis, J., et al. (2004). Multiple interactions between regulatory regions are required to stabilize an active chromatin hub. Genes & Development, 18, 1495–1509.

    Article  CAS  Google Scholar 

  • Paul, F., Arkin, Y., Giladi, A., Jaitin, D. A., Kenigsberg, E., Keren-Shaul, H., et al. (2015). Transcriptional heterogeneity and lineage commitment in myeloid progenitors. Cell, 163, 1663–1677.

    Article  CAS  PubMed  Google Scholar 

  • Pencovich, N., Jaschek, R., Tanay, A., & Groner, Y. (2011). Dynamic combinatorial interactions of RUNX1 and cooperating partners regulates megakaryocytic differentiation in cell line models. Blood, 117, e1–14.

    Article  CAS  PubMed  Google Scholar 

  • Pozner, A., Goldenberg, D., Negreanu, V., Le, S. Y., Elroy-Stein, O., Levanon, D., & Groner, Y. (2000). Transcription-coupled translation control of AML1/RUNX1 is mediated by cap- and internal ribosome entry site-dependent mechanisms. Molecular and Cellular Biology, 20, 2297–2307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pozner, A., Lotem, J., Xiao, C., Goldenberg, D., Brenner, O., Negreanu, V., et al. (2007). Developmentally regulated promoter-switch transcriptionally controls Runx1 function during embryonic hematopoiesis. BMC Developmental Biology, 7, 84.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ptasinska, A., Assi, S. A., Mannari, D., James, S. R., Williamson, D., Dunne, J., et al. (2012). Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding. Leukemia, 26, 1829–1841.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ptasinska, A., Assi, S. A., Martinez-Soria, N., Imperato, M. R., Piper, J., Cauchy, P., et al. (2014). Identification of a dynamic core transcriptional network in t(8;21) AML that regulates differentiation block and self-renewal. Cell Reports, 8, 1974–1988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Putz, G., Rosner, A., Nuesslein, I., Schmitz, N., & Buchholz, F. (2006). AML1 deletion in adult mice causes splenomegaly and lymphomas. Oncogene, 25, 929–939.

    Article  CAS  PubMed  Google Scholar 

  • Ran, D., Shia, W.-J., Lo, M.-C., Fan, J.-B., Knorr, D. A., Ferrell, P. I., et al. (2013). RUNX1a enhances hematopoietic lineage commitment from human embryonic stem cells and inducible pluripotent stem cells. Blood, 121, 2882–2890.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reed-Inderbitzin, E., Moreno-Miralles, I., Vanden-Eynden, S. K., Xie, J., Lutterbach, B., Durst-Goodwin, K. L., et al. (2006). RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription. Oncogene, 25, 5777–5786.

    Article  CAS  PubMed  Google Scholar 

  • Regha, K., Assi, S. A., Tsoulaki, O., Gilmour, J., Lacaud, G., & Bonifer, C. (2015). Developmental-stage-dependent transcriptional response to leukaemic oncogene expression. Nature Communications, 6, 7203.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rennert, J., Coffman, J. A., Mushegian, A. R., & Robertson, A. J. (2003). The evolution of Runx genes I. A comparative study of sequences from phylogenetically diverse model organisms. BMC Evolutionary Biology, 3, 4.

    Article  PubMed  PubMed Central  Google Scholar 

  • Ross, K., Sedello, A. K., Todd, G. P., Paszkowski-Rogacz, M., Bird, A. W., Ding, L., et al. (2012). Polycomb group ring finger 1 cooperates with Runx1 in regulating differentiation and self-renewal of hematopoietic cells. Blood, 119, 4152–4161.

    Article  CAS  PubMed  Google Scholar 

  • Scott, E. W., Simon, M. C., Anastasi, J., & Singh, H. (1994). Requirement of transcription factor PU.1 in the development of multiple hematopoietic lineages. Science, 265, 1573–1577.

    Article  CAS  PubMed  Google Scholar 

  • Sellars, M., Huh, J. R., Day, K., Issuree, P. D., Galan, C., Gobeil, S., et al. (2015). Regulation of DNA methylation dictates Cd4 expression during the development of helper and cytotoxic T cell lineages. Nature Immunology, 16, 746–754.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shang, Y., Zhao, X., Xu, X., Xin, H., Li, X., Zhai, Y., et al. (2009). CHIP functions an E3 ubiquitin ligase of Runx1. Biochemical and Biophysical Research Communications, 386, 242–246.

    Article  CAS  PubMed  Google Scholar 

  • Song, W. J., Sullivan, M. G., Legare, R. D., Hutchings, S., Tan, X., Kufrin, D., et al. (1999). Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nature Genetics, 23, 166–175.

    Article  CAS  PubMed  Google Scholar 

  • Sroczynska, P., Lancrin, C., Kouskoff, V., & Lacaud, G. (2009). The differential activities of Runx1 promoters define milestones during embryonic hematopoiesis. Blood, 114, 5279–5289.

    Article  CAS  PubMed  Google Scholar 

  • Staber, P. B., Zhang, P., Ye, M., Welner, R. S., Levantini, E., Di Ruscio, A., et al. (2014). The Runx-PU.1 pathway preserves normal and AML/ETO9a leukemic stem cells. Blood, 124, 2391–2399.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stopka, T., Amanatullah, D. F., Papetti, M., & Skoultchi, A. I. (2005). PU.1 inhibits the erythroid program by binding to GATA-1 on DNA and creating a repressive chromatin structure. The EMBO Journal, 24, 3712–3723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sun, X. J., Wang, Z., Wang, L., Jiang, Y., Kost, N., Soong, T. D., et al. (2013). A stable transcription factor complex nucleated by oligomeric AML1-ETO controls leukaemogenesis. Nature, 500, 93–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka, T., Tanaka, K., Ogawa, S., Kurokawa, M., Mitani, K., Nishida, J., et al. (1995). An acute myeloid leukemia gene, AML1, regulates hemopoietic myeloid cell differentiation and transcriptional activation antagonistically by two alternative spliced forms. The EMBO Journal, 14, 341–350.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tanaka, T., Kurokawa, M., Ueki, K., Tanaka, K., Imai, Y., Mitani, K., et al. (1996). The extracellular signal-regulated kinase pathway phosphorylates AML1, an acute myeloid leukemia gene product, and potentially regulates its transactivation ability. Molecular and Cellular Biology, 16, 3967–3979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taniuchi, I., Osato, M., Egawa, T., Sunshine, M. J., Bae, S. C., Komori, T., et al. (2002). Differential requirements for Runx proteins in CD4 repression and epigenetic silencing during T lymphocyte development. Cell, 111, 621–633.

    Article  CAS  PubMed  Google Scholar 

  • Telfer, J. (2001). Expression and function of a stem cell promoter for the murine CBFα2 gene: Distinct roles and regulation in natural killer and T cell development. Developmental Biology, 229, 363–382.

    Article  CAS  PubMed  Google Scholar 

  • Theo Sijtse Palstra, R. J. (2009). Close encounters of the 3C kind: Long-range chromatin interactions and transcriptional regulation. Briefings in Functional Genomics & Proteomics, 8, 297–309.

    Article  CAS  Google Scholar 

  • Tolhuis, B., Palstra, R. J., Splinter, E., Grosveld, F., & de Laat, W. (2002). Looping and interaction between hypersensitive sites in the active beta-globin locus. Molecular Cell, 10, 1453–1465.

    Article  CAS  PubMed  Google Scholar 

  • Trombly, D. J., Whitfield, T. W., Padmanabhan, S., Gordon, J. A., Lian, J. B., van Wijnen, A. J., et al. (2015). Genome-wide co-occupancy of AML1-ETO and N-CoR defines the t(8;21) AML signature in leukemic cells. BMC Genomics, 16, 309.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Tsuzuki, S., & Seto, M. (2012). Expansion of functionally defined mouse hematopoietic stem and progenitor cells by a short isoform of RUNX1/AML1. Blood, 119, 727–735.

    Article  CAS  PubMed  Google Scholar 

  • Tsuzuki, S., Hong, D., Gupta, R., Matsuo, K., Seto, M., & Enver, T. (2007). Isoform-specific potentiation of stem and progenitor cell engraftment by AML1/RUNX1. PLoS Medicine, 4, e172.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • van Oevelen, C., Collombet, S., Vicent, G., Hoogenkamp, M., Lepoivre, C., Badeaux, A., et al. (2015). C/EBPalpha activates pre-existing and de novo macrophage enhancers during induced Pre-B cell transdifferentiation and myelopoiesis. Stem Cell Reports, 5, 232–247.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • van Riel, B., Pakozdi, T., Brouwer, R., Monteiro, R., Tuladhar, K., Franke, V., et al. (2012). A novel complex, RUNX1-MYEF2, represses hematopoietic genes in erythroid cells. Molecular and Cellular Biology, 32, 3814–3822.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Vernimmen, D., De Gobbi, M., Sloane-Stanley, J. A., Wood, W. G., & Higgs, D. R. (2007). Long-range chromosomal interactions regulate the timing of the transition between poised and active gene expression. The EMBO Journal, 26, 2041–2051.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, Q., Stacy, T., Binder, M., Marín-Padilla, M., Sharpe, A. H., & Speck, N. A. (1996). Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proceedings of the National Academy of Sciences of the United States of America, 93, 3444–3449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wee, H.-J., Voon, D. C.-C., Bae, S. C., & Ito, Y. (2008). PEBP2-beta/CBF-beta-dependent phosphorylation of RUNX1 and p300 by HIPK2: Implications for leukemogenesis. Blood, 112, 3777–3787.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wheeler, J. C., Shigesada, K., Gergen, J. P., & Ito, Y. (2000). Mechanisms of transcriptional regulation by Runt domain proteins. Seminars in Cell and Developmental Biology, 11, 369–375.

    Article  CAS  PubMed  Google Scholar 

  • Williams, A. O., Isaacs, R. J., & Stowell, K. M. (2007). Down-regulation of human topoisomerase IIalpha expression correlates with relative amounts of specificity factors Sp1 and Sp3 bound at proximal and distal promoter regions. BMC Molecular Biology, 8, 36.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wilson, N. K., Foster, S. D., Wang, X., Knezevic, K., Schutte, J., Kaimakis, P., et al. (2010). Combinatorial transcriptional control in blood stem/progenitor cells: Genome-wide analysis of ten major transcriptional regulators. Cell Stem Cell, 7, 532–544.

    Article  CAS  PubMed  Google Scholar 

  • Wotton, D., Ghysdael, J., Wang, S., Speck, N. A., & Owen, M. J. (1994). Cooperative binding of Ets-1 and core binding factor to DNA. Molecular and Cellular Biology, 14, 840–850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamaguchi, Y., Kurokawa, M., Imai, Y., Izutsu, K., Asai, T., Ichikawa, M., et al. (2004). AML1 is functionally regulated through p300-mediated acetylation on specific lysine residues. The Journal of Biological Chemistry, 279, 15630–15638.

    Article  CAS  PubMed  Google Scholar 

  • Yergeau, D. A., Hetherington, C. J., Wang, Q., Zhang, P., Sharpe, A. H., Binder, M., et al. (1997). Embryonic lethality and impairment of haematopoiesis in mice heterozygous for an AML1-ETO fusion gene. Nature Genetics, 15, 303–306.

    Article  CAS  PubMed  Google Scholar 

  • Yu, M., Mazor, T., Huang, H., Huang, H.-T., Kathrein, K. L., Woo, A. J., et al. (2012). Direct recruitment of polycomb repressive complex 1 to chromatin by core binding transcription factors. Molecular Cell, 45, 330–343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaidi, S. K., Javed, A., Choi, J. Y., van Wijnen, A. J., Stein, J. L., Lian, J. B., & Stein, G. S. (2001). A specific targeting signal directs Runx2/Cbfa1 to subnuclear domains and contributes to transactivation of the osteocalcin gene. Journal of Cell Science, 114, 3093–3102.

    CAS  PubMed  Google Scholar 

  • Zaidi, S. K., Sullivan, A. J., van Wijnen, A. J., Stein, J. L., Stein, G. S., & Lian, J. B. (2002). Integration of Runx and Smad regulatory signals at transcriptionally active subnuclear sites. Proceedings of the National Academy of Sciences of the United States of America, 99, 8048–8053.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaidi, S. K., Young, D. W., Pockwinse, S. M., Javed, A., Lian, J. B., Stein, J. L., et al. (2003). Mitotic partitioning and selective reorganization of tissue-specific transcription factors in progeny cells. Proceedings of the National Academy of Sciences of the United States of America, 100, 14852–14857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zambidis, E. T. (2005). Hematopoietic differentiation of human embryonic stem cells progresses through sequential hematoendothelial, primitive, and definitive stages resembling human yolk sac development. Blood, 106, 860–870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zaret, K. S. (2014). Genome reactivation after the silence in mitosis: Recapitulating mechanisms of development? Developmental Cell, 29, 132–134.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeng, C., van Wijnen, A. J., Stein, J. L., Meyers, S., Sun, W., Shopland, L., et al. (1997). Identification of a nuclear matrix targeting signal in the leukemia and bone-related AML/CBF-alpha transcription factors. Proceedings of the National Academy of Sciences of the United States of America, 94, 6746–6751.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeng, C., McNeil, S., Pockwinse, S., Nickerson, J., Shopland, L., Lawrence, J. B., et al. (1998). Intranuclear targeting of AML/CBFalpha regulatory factors to nuclear matrix-associated transcriptional domains. Proceedings of the National Academy of Sciences of the United States of America, 95, 1585–1589.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, D. E., Zhang, P., Wang, N. D., Hetherington, C. J., Darlington, G. J., & Tenen, D. G. (1997). Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. Proceedings of the National Academy of Sciences of the United States of America, 94, 569–574.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, D. E., Petrovick, M. S., Hiebert, S. W., Friedman, A. D., Hetherington, C. J., & Tenen, D. G. (1998). Multiple functional domains of AML1: PU.1 and C/EBPalpha synergize with different regions of AML1. Molecular and Cellular Biology, 18, 3915–3925.

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang, L., Fried, F. B., Guo, H., & Friedman, A. D. (2008). Cyclin-dependent kinase phosphorylation of RUNX1/AML1 on 3 sites increases transactivation potency and stimulates cell proliferation. Blood, 111, 1193–1200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang, H., Alberich-Jorda, M., Amabile, G., Yang, H., Staber, P. B., Di Ruscio, A., et al. (2013). Sox4 is a key oncogenic target in C/EBPalpha mutant acute myeloid leukemia. Cancer Cell, 24, 575–588.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao, X., Jankovic, V., Gural, A., Huang, G., Pardanani, A., Menendez, S., et al. (2008). Methylation of RUNX1 by PRMT1 abrogates SIN3A binding and potentiates its transcriptional activity. Genes & Development, 22, 640–653.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Work in Constanze Bonifer’s lab is supported by grants from Bloodwise, the BBSRC and the Kay Kendall Leukemia fund. Georges Lacaud and Valerie Kouskoff are funded by the BBSRC, MRC, Bloodwise and Cancer Research UK.

Author information

Authors and Affiliations

  1. Institute for Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK

    Constanze Bonifer

  2. Beth Israel Diaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Elena Levantini

  3. Istituto di Tecnologie Biomediche, Consiglio Nazionale delle Richerche, Pisa, Italy

    Elena Levantini

  4. Division of Developmental Biology & Medicine, The University of Manchester, Manchester, UK

    Valerie Kouskoff

  5. Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK

    Georges Lacaud

Authors
  1. Constanze Bonifer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elena Levantini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valerie Kouskoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Georges Lacaud
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Constanze Bonifer .

Editor information

Editors and Affiliations

  1. Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

    Yoram Groner

  2. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    Yoshiaki Ito

  3. Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA

    Paul Liu

  4. Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom

    James C. Neil

  5. Department of Cell and Development Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Nancy A. Speck

  6. Mayo Clinic, Rochester, Minnesota, USA

    Andre van Wijnen

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Nature Singapore Pte Ltd.

About this chapter

Cite this chapter

Bonifer, C., Levantini, E., Kouskoff, V., Lacaud, G. (2017). Runx1 Structure and Function in Blood Cell Development. In: Groner, Y., Ito, Y., Liu, P., Neil, J., Speck, N., van Wijnen, A. (eds) RUNX Proteins in Development and Cancer. Advances in Experimental Medicine and Biology, vol 962. Springer, Singapore. https://doi.org/10.1007/978-981-10-3233-2_5

Download citation

Publish with us

Policies and ethics

Search

Navigation