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Spatiotemporal expression pattern of Mirg, an imprinted non-coding gene, during mouse embryogenesis

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Abstract

Recent research has revealed that the maternal non-coding RNA genes (Gtl2, Rian and Mirg) from the Dlk1-Dio3 imprinted cluster are closely related to the full development potential of the induced pluripotent stem cells (iPSCs). Transcriptional silencing of these genes failed to generate all-iPSC mice, indicating their significant contribution to embryogenesis. However, except for Gtl2, little information regarding these genes has been acquired in this cluster. In the present study, we analyzed the spatiotemporal expression patterns of Mirg during mouse embryogenesis. Using in situ hybridization and quantitative PCR, we demonstrated that Mirg non-coding RNA exhibited sustained expression throughout mouse embryogenesis from E8.5 to E18.5. Strong expression was detected in the central nervous system (E9.5–E15.5) and various skeletal muscles (E13.5 and E15.5), and the subcellular localization appeared to be in the nuclei. The pituitary and adrenal gland also showed high expression of Mirg, but, unlike the skeletal muscles and the neural circuitry, the signals were not concentrated in the nuclei. In the major internal organs, Mirg maintained low expression during embryogenesis (E12.5–E18.5) whereas in the liver and the developing lung, Mirg was expressed with a gradually decreasing trend and a gradually raising trend, respectively. These findings indicate that temporal regulation of Mirg expression may be required during specific stages and in specific tissues during embryonic development.

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Abbreviations

Mirg :

miRNA containing gene

Dlk1-Gtl2 :

Delta like homolog 1-gene trap locus2

lncRNA:

Long non-coding RNA

Rian :

RNA imprinted and accumulated in the nucleus

anti-Rtl1 :

anti-retrotransposon-like 1

Rtl1 :

Retrotransposon-like 1

Dio3 :

Deiodinase iodothyronine type III

MEGs:

The maternally expressed genes

iPSCs:

The induced pluripotent stem cells

CNS:

The central nervous system

References

  • Byrne K, Colgrave ML, Vuocolo T, Pearson R, Bidwell CA, Cockett NE, Lynn DJ, Fleming-Waddell JN, Tellam RL (2010) The imprinted retrotransposon-like gene PEG11 (RTL1) is expressed as a full-length protein in skeletal muscle from Callipyge sheep. PloS one 5(1):e8638. doi:10.1371/journal.pone.0008638

    Article  PubMed  Google Scholar 

  • Cavaille J, Seitz H, Paulsen M, Ferguson-Smith AC, Bachellerie JP (2002) Identification of tandemly-repeated C/D snoRNA genes at the imprinted human 14q32 domain reminiscent of those at the Prader-Willi/Angelman syndrome region. Hum Mol Genet 11(13):1527–1538

    Article  PubMed  CAS  Google Scholar 

  • Charalambous M, da Rocha ST, Ferguson-Smith AC (2007) Genomic imprinting, growth control and the allocation of nutritional resources: consequences for postnatal life. Curr Opin Endocrinol Diabetes Obes 14(1):3–12. doi:10.1097/MED.0b013e328013daa2

    Article  PubMed  CAS  Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 162(1):156–159. doi:10.1006/abio.1987.9999

    Article  PubMed  CAS  Google Scholar 

  • da Rocha ST, Tevendale M, Knowles E, Takada S, Watkins M, Ferguson-Smith AC (2007) Restricted co-expression of Dlk1 and the reciprocally imprinted non-coding RNA, Gtl2: implications for cis-acting control. Dev Biol 306(2):810–823

    Article  PubMed  CAS  Google Scholar 

  • da Rocha ST, Edwards CA, Ito M, Ogata T, Ferguson-Smith AC (2008) Genomic imprinting at the mammalian Dlk1-Dio3 domain. Trends Genet 24(6):306–316

    Article  PubMed  Google Scholar 

  • Georgiades P, Watkins M, Surani MA, Ferguson-Smith AC (2000) Parental origin-specific developmental defects in mice with uniparental disomy for chromosome 12. Development 127(21):4719–4728

    PubMed  CAS  Google Scholar 

  • Ginger MR, Shore AN, Contreras A, Rijnkels M, Miller J, Gonzalez-Rimbau MF, Rosen JM (2006) A noncoding RNA is a potential marker of cell fate during mammary gland development. Proc Natl Acad Sci USA 103(15):5781–5786

    Article  PubMed  CAS  Google Scholar 

  • Hagan JP, O’Neill BL, Stewart CL, Kozlov SV, Croce CM (2009) At least ten genes define the imprinted Dlk1-Dio3 cluster on mouse chromosome 12qF1. PloS one 4(2):e4352. doi:10.1371/journal.pone.0004352

    Article  PubMed  Google Scholar 

  • Hatada I, Morita S, Obata Y, Sotomaru Y, Shimoda M, Kono T (2001) Identification of a new imprinted gene, Rian, on mouse chromosome 12 by fluorescent differential display screening. J Biochem 130(2):187–190

    PubMed  CAS  Google Scholar 

  • Hernandez A, Fiering S, Martinez E, Galton VA, St Germain D (2002) The gene locus encoding iodothyronine deiodinase type 3 (Dio3) is imprinted in the fetus and expresses antisense transcripts. Endocrinology 143(11):4483–4486

    Article  PubMed  CAS  Google Scholar 

  • Hutchinson JN, Ensminger AW, Clemson CM, Lynch CR, Lawrence JB, Chess A (2007) A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics 8:39

    Article  PubMed  Google Scholar 

  • Liu L, Luo GZ, Yang W, Zhao X, Zheng Q, Lv Z, Li W, Wu HJ, Wang L, Wang XJ, Zhou Q (2010) Activation of the imprinted Dlk1-Dio3 region correlates with pluripotency levels of mouse stem cells. J Biol Chem

  • Mercer TR, Dinger ME, Sunkin SM, Mehler MF, Mattick JS (2008) Specific expression of long noncoding RNAs in the mouse brain. Proc Natl Acad Sci USA 105(2):716–721

    Article  PubMed  CAS  Google Scholar 

  • Miyoshi N, Wagatsuma H, Wakana S, Shiroishi T, Nomura M, Aisaka K, Kohda T, Surani MA, Kaneko-Ishino T, Ishino F (2000) Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q. Genes Cells 5(3):211–220

    Article  PubMed  CAS  Google Scholar 

  • Olivier B, Walter W (1998) A simplified in situ hybridization protocol using non-radioactivety labeled probes to detect abundant and rare mRNAs on tissue sections. Biochemica 1:10–16

    Google Scholar 

  • Schmidt JV, Matteson PG, Jones BK, Guan XJ, Tilghman SM (2000) The Dlk1 and Gtl2 genes are linked and reciprocally imprinted. Genes Dev 14(16):1997–2002

    PubMed  CAS  Google Scholar 

  • Schuster-Gossler K, Bilinski P, Sado T, Ferguson-Smith A, Gossler A (1998) The mouse Gtl2 gene is differentially expressed during embryonic development, encodes multiple alternatively spliced transcripts, and may act as an RNA. Dev Dyn 212(2):214–228

    Article  PubMed  CAS  Google Scholar 

  • Seitz H, Youngson N, Lin SP, Dalbert S, Paulsen M, Bachellerie JP, Ferguson-Smith AC, Cavaille J (2003) Imprinted microRNA genes transcribed antisense to a reciprocally imprinted retrotransposon-like gene. Nat Genet 34(3):261–262. doi:10.1038/ng1171

    Article  PubMed  CAS  Google Scholar 

  • Seitz H, Royo H, Bortolin ML, Lin SP, Ferguson-Smith AC, Cavaille J (2004) A large imprinted microRNA gene cluster at the mouse Dlk1-Gtl2 domain. Genome Res 14(9):1741–1748

    Article  PubMed  CAS  Google Scholar 

  • Stadtfeld M, Apostolou E, Akutsu H, Fukuda A, Follett P, Natesan S, Kono T, Shioda T, Hochedlinger K (2010) Aberrant silencing of imprinted genes on chromosome 12qF1 in mouse induced pluripotent stem cells. Nature 465(7295):175–181

    Article  PubMed  CAS  Google Scholar 

  • Sutton VR, McAlister WH, Bertin TK, Kaffe S, Wang JC, Yano S, Shaffer LG, Lee B, Epstein CJ, Villar AJ (2003) Skeletal defects in paternal uniparental disomy for chromosome 14 are re-capitulated in the mouse model (paternal uniparental disomy 12). Hum Genet 113(5):447–451. doi:10.1007/s00439-003-0981-x

    Article  PubMed  Google Scholar 

  • Takada S, Tevendale M, Baker J, Georgiades P, Campbell E, Freeman T, Johnson MH, Paulsen M, Ferguson-Smith AC (2000) Delta-like and gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12. Curr Biol 10(18):1135–1138

    Article  PubMed  CAS  Google Scholar 

  • Takahashi N, Okamoto A, Kobayashi R, Shirai M, Obata Y, Ogawa H, Sotomaru Y, Kono T (2009) Deletion of Gtl2, imprinted non-coding RNA, with its differentially methylated region induces lethal parent-origin-dependent defects in mice. Hum Mol Genet 18(10):1879–1888

    Article  PubMed  CAS  Google Scholar 

  • Tierling S, Dalbert S, Schoppenhorst S, Tsai CE, Oliger S, Ferguson-Smith AC, Paulsen M, Walter J (2006) High-resolution map and imprinting analysis of the Gtl2-Dnchc1 domain on mouse chromosome 12. Genomics 87(2):225–235

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson LS, Davies W, Isles AR (2007) Genomic imprinting effects on brain development and function. Nat Rev Neurosci 8(11):832–843

    Article  PubMed  CAS  Google Scholar 

  • Wu Q, Kumagai T, Kawahara M, Ogawa H, Hiura H, Obata Y, Takano R, Kono T (2006) Regulated expression of two sets of paternally imprinted genes is necessary for mouse parthenogenetic development to term. Reproduction 131(3):481–488

    Article  PubMed  CAS  Google Scholar 

  • Zhou Y, Cheunsuchon P, Nakayama Y, Lawlor MW, Zhong Y, Rice KA, Zhang L, Zhang X, Gordon FE, Lidov HG, Bronson RT, Klibanski A (2010) Activation of paternally expressed genes and perinatal death caused by deletion of the Gtl2 gene. Development 137(16):2643–2652

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported from the National Natural Science Foundation of China (No. 30971645), Heilongjiang Province Technological Project Program Returning Foundation (No. LC08C05), State Key Laboratory of Urban Water Resource and Environment (Grant No. 2010TS05) and Project (HIT. NSRIF. 2009088) Supported by Natural Scientific Research Innovation Foundation in Harbin Institute of Technology.

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Authors and Affiliations

  1. Department of Life Science and Engineering, State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, No.92 West Da-zhi Street, Harbin, Heilongjiang, China

    Zhengbin Han, Hongjuan He, Fengwei Zhang, Zhijun Huang & Qiong Wu

  2. Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa-ku, Nagoya, 464-8602, Japan

    Ziguang Liu

  3. College of Life Sciences, LuDong University, YanTai, Shandong, China

    Huijie Jiang

  4. Cell Therapy Program, Princess Margaret Hospital, Room 4-605, 610 University Avenue, Toronto, ON, M5G 2M9, Canada

    Huijie Jiang

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  1. Zhengbin Han
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  2. Hongjuan He
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Correspondence to Qiong Wu.

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Han, Z., He, H., Zhang, F. et al. Spatiotemporal expression pattern of Mirg, an imprinted non-coding gene, during mouse embryogenesis. J Mol Hist 43, 1–8 (2012). https://doi.org/10.1007/s10735-011-9367-x

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  • DOI: https://doi.org/10.1007/s10735-011-9367-x

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