Abstract

Mammalian germ cells undergo global reprogramming of DNA methylation during their development. Global DNA demethylation occurs around the time when the primordial germ cells colonize the embryonic gonads and this coincides with dynamic changes in chromatin composition. Global de novo DNA methylation takes place with remarkably different dynamics between the two sexes, prospermatogonia attaining methylation during fetal stages and oocytes attaining methylation postnatally. Our hypothesis was that dynamic changes in chromatin composition may precede or accompany the wave of global DNA de novo methylation as well. We used immunocytochemistry to measure global DNA methylation and chromatin components in male and female mouse fetal germ cells compared to control somatic cells of the gonad. We found that global DNA methylation levels sharply increased in male germ cells at 17.5 days post coitum, but remained low in female germ cells at all fetal stages. Global changes in chromatin composition: i, preceded global DNA methylation in fetal germ cells; ii, sex specifically occurred in male but not in female germ cells; iii, affected active and repressive histone marks and iv, included histone tail and histone globular domain modifications. Our data suggest that dynamic changes of chromatin composition may provide a framework for the pattern of male-specific de novo DNA methylation in prospermatogonia.

Highlights

  • Global waves of epigenetic changes during development At two times during development, in the germ line and during preimplantation, the epigenome of mammals undergoes global resetting [1,2,3]

  • About global chromatin changes during fetal germ cell development, and the information is limited to spatial reorganization of heterochromatin components H3K9me3 and CBX5 (HP1a) [10]

  • Dynamic global chromatin changes in fetal germ cells The major finding of this study is that chromatin undergoes dynamic global changes in male fetal germ cells at the time of global DNA methylation reprogramming (Figure 10)

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Summary

Introduction

Global waves of epigenetic changes during development At two times during development, in the germ line and during preimplantation, the epigenome of mammals undergoes global resetting [1,2,3]. Global demethylation occurs in primordial germ cells (PGCs) around the time when they colonize the genital ridges. Global de novo DNA methylation occurs with different dynamics between the two sexes. Immunostaining experiments revealed that dynamic and orderly chromatin changes take place in PGCs at the time of their specifications and during the time when DNA methylation erasure occurs [6,7,8,9,10]. About global chromatin changes during fetal germ cell development, and the information is limited to spatial reorganization of heterochromatin components H3K9me and CBX5 (HP1a) [10]

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