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X-inactivation and X-reactivation: epigenetic hallmarks of mammalian reproduction and pluripotent stem cells

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Abstract

X-chromosome inactivation is an epigenetic hallmark of mammalian development. Chromosome-wide regulation of the X-chromosome is essential in embryonic and germ cell development. In the male germline, the X-chromosome goes through meiotic sex chromosome inactivation, and the chromosome-wide silencing is maintained from meiosis into spermatids before the transmission to female embryos. In early female mouse embryos, X-inactivation is imprinted to occur on the paternal X-chromosome, representing the epigenetic programs acquired in both parental germlines. Recent advances revealed that the inactive X-chromosome in both females and males can be dissected into two elements: repeat elements versus unique coding genes. The inactive paternal X in female preimplantation embryos is reactivated in the inner cell mass of blastocysts in order to subsequently allow the random form of X-inactivation in the female embryo, by which both Xs have an equal chance of being inactivated. X-chromosome reactivation is regulated by pluripotency factors and also occurs in early female germ cells and in pluripotent stem cells, where X-reactivation is a stringent marker of naive ground state pluripotency. Here we summarize recent progress in the study of X-inactivation and X-reactivation during mammalian reproduction and development as well as in pluripotent stem cells.

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Acknowledgments

We thank Yuya Ogawa, Yesu Jeon and Ho-Su Sin for critical reading and Erin L. Adams for editing of the manuscript. This work was supported by a fellowship of the International Human Frontier Science Program Organization (HFSP) to B.P., an NIH grant (RO1-GM58839) to J.T.L, and the Developmental Fund and Trustee Grant at Cincinnati Children’s Hospital Medical Center to S.H.N. J.T.L. is an investigator of the Howard Hughes Medical Institute.

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  1. Department of Genetics, Harvard Medical School, Boston, MA, USA

    Bernhard Payer & Jeannie T. Lee

  2. Howard Hughes Medical Institute, Boston, MA, USA

    Bernhard Payer & Jeannie T. Lee

  3. Department of Molecular Biology, Massachusetts General Hospital, Boston, MA, USA

    Bernhard Payer & Jeannie T. Lee

  4. Division of Reproductive Sciences, Perinatal Institute, Cincinnati Children’s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA

    Satoshi H. Namekawa

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  1. Bernhard Payer
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Correspondence to Bernhard Payer or Satoshi H. Namekawa.

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Payer, B., Lee, J.T. & Namekawa, S.H. X-inactivation and X-reactivation: epigenetic hallmarks of mammalian reproduction and pluripotent stem cells. Hum Genet 130, 265–280 (2011). https://doi.org/10.1007/s00439-011-1024-7

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