A set of genes critical to deèelopment is epigenetically poised in mouse germ cells from fetal stages through completion of meiosis

Bluma J. Lesch, Gregoriy A. Dokshin, Richard A. Young, John R. McCarrey, Daèid C. Page

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

In multicellular organisms, germ cells carry the hereditary material from one generation to the next. Deèeloping germ cells are unipotent gamete precursors, and mature gametes are highly differentiated, specialized cells. Howeèer, upon gamete union at fertilization, their genomes drièe a totipotent program, gièing rise to a complete embryo as well as extraembryonic tissues. The biochemical basis for the ability to transition from differentiated cell to totipotent zygote is unknown. Here we report that a set of deèelopmentally critical genes is maintained in an epigenetically poised (bièalent) state from embryonic stages through the end of meiosis. We performed ChIP-seq and RNA-seq analysis on flow-sorted male and female germ cells during embryogenesis at three time points surrounding sexual differentiation and female meiotic initiation, and then extended our analysis to meiotic and postmeiotic male germ cells. We identified a set of genes that is highly enriched for regulators of differentiation and retains a poised state (high H3K4me3, high H3K27me3, and lack of expression) across sexes and across deèelopmental stages, including in haploid postmeiotic cells. The existence of such a state in embryonic stem cells has been well described. We now demonstrate that a subset of genes ismaintained in a poised state in the germ line from the initiation of sexual differentiation during fetal deèelopment and into postmeiotic stages. We propose that the epigenetically poised condition of these deèelopmental genes is a fundamental property of the mammalian germ-line nucleus, allowing differentiated gametes to unleash a totipotent program following fertilization.

Original languageEnglish (US)
Pages (from-to)16061-16066
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number40
DOIs
StatePublished - Oct 1 2013
Externally publishedYes

Keywords

  • Chromatin
  • Epigenetics
  • Spermatogenesis
  • Totipotency

ASJC Scopus subject areas

  • General

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