Sex-Specific Histone Modifications in Mouse Fetal and Neonatal Germ Cells

Abstract

Epigenetic signatures of germline cells are dynamically reprogrammed to induce appropriate differentiation, development and sex specification. We investigated sex-specific epigenetic changes in mouse fetal germ cells (FGCs) and neonatal germ cells. Materials & methods: Six histone marks in mouse E13.5 FGCs and P1 neonatal germ cells were analyzed by chromatin immunoprecipitation and sequencing. These datasets were compared with transposase-accessible chromatin sites, DNA methylation and transcriptome. Results: Different patterns of each histone mark were detected in female and male FGCs, and H3K4me3/H3K27me3 bivalent marks were enriched in different chromosomal regions of female and male FGCs. Conclusion: Our results suggest that histone modifications may affect FGC gene expression following DNA methylation erasure, contributing to the differentiation into female and male germ cells.

Paternal MTHFR deficiency leads to hypomethylation of young retrotransposons and reproductive decline across two successive generations

“…As H3K4me3 is known to block DNA methylation due to its binding preference of the ADD domain of DNMT3L towards unmethylated H3K4 ( Zhang et al, 2010 ), the presence of this histone mark is a plausible candidate for explaining the delayed acquisition of DNA methylation marks at MTHFR-sensitive sequences. We used published chromatin immunoprecipitation (ChIP) sequencing data on isolated E10.5, E13.5 and E16.5 male germ cells to compare H3K4me3 enrichment at a genome-wide level versus that for sequences affected by MTHFR deficiency ( Kawabata et al, 2019 ; Shirane et al, 2020 ). Compared with the whole genome, where H3K4me3 was relatively stable, MTHFR-sensitive sequences showed increased levels of H3K4me3 in 1-kb bins from E13.5 to E16.5 ( Fig.…”

“…WGBS data were derived from E13.5 male PGCs, E16.5 PSG ( Kobayashi et al, 2013 ), P0 PSG, spermatozoa ( Kubo et al, 2015 ), spermatocyte ( Hammoud et al, 2014 ), Nsd1 HET and KO P0 PSG ( Shirane et al, 2020 ) and Dnmt3c and Dnmt3l KO P10 germ cells with matching controls ( Barau et al, 2016 ). H3K4me3 ChIP-seq data were derived from E10.5 and E13.5 male PGCs ( Kawabata et al, 2019 ), E16.5 and P0 PSG ( Shirane et al, 2020 ), spermatocyte ( Baker et al, 2014 ) and spermatozoa ( Erkek et al, 2013 ). RNA-seq data were derived from Dnmt3c and Dnmt3l KO P10 germ cells with matching controls ( Barau et al, 2016 ).…”

The Beginning of Meiosis in Mammalian Female Germ Cells: A Never-Ending Story of Intrinsic and Extrinsic Factors

“…As noted, among the repressive histones, the decrease in H3K27me3 is followed by an increase from 12.5 to 16.5 dpc concomitant with the beginning of meiosis in female germ cells [ 54 ], suggesting that a high level of this histone may be necessary for meiotic entry. Notably, histone modifications seem to be, at least in part, sex specific [ 55 ]. Interestingly, mouse PGCs obtained from 11.5–13.5 dpc specimens of both sexes revealed H3K4me3/H3K27me3 bivalent domains to be highly enriched at the developmental regulatory genes in a manner remarkably similar to that of embryonic stem cells (ESCs) [ 56 ].…”

Disruption of piRNA machinery by deletion of ASZ1/GASZ results in the expression of aberrant chimeric transcripts in gonocytes

“…Chromatin immunoprecipitation sequencing (ChIP-seq) data were downloaded from DRA006633 [ 39 ]. ChIP-seq reads were trimmed using Trimmomatic (version 0.36), and only paired reads were subjected to subsequent analyses.…”