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Setdb1 is essential for meiotic sex chromosome inactivation in mice

ABSTRACT: Meiotic synapsis and recombination ensure correct homologous segregation and genetic diversity. Asynapsed homologues are transcriptionally inactivated by meiotic silencing, which serves a surveillance function and in males drives meiotic sex chromosome inactivation. Silencing depends on the DNA damage response (DDR) network, but how DDR proteins engage repressive chromatin marks is unknown. We identify the histone H3-lysine-9 methyltransferase SETDB1 as the bridge linking the DDR to silencing in male mice. At the onset of silencing, X-chromosome H3K9 trimethylation (H3K9me3) enrichment is downstream of DDR factors. Without Setdb1, the X chromosome accrues DDR proteins but not H3K9me3. Consequently, sex chromosome remodelling and silencing fails, causing germ cell apoptosis. Our data implicate TRIM28 in linking the DDR to SETDB1, and uncover additional factors with putative meiotic XY-silencing functions. Furthermore, we show that SETDB1 imposes timely expression of meiotic and post-meiotic genes. Setdb1 thus unites the DDR network, asynapsis and meiotic chromosome silencing.

ORGANISM(S): Mus musculus

PROVIDER: GSE107671 | GEO | 2018/11/01

REPOSITORIES: GEO

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MCAF2/ATF7IP2 directs meiosis-specific H3K9 methylation

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AGO4 Regulates Entry into Meiosis and Influences Silencing of Sex Chromosomes in the Male Mouse Germline

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Setdb1 is essential for meiotic sex chromosome inactivation in mice

Project description:Setdb1 is essential for meiotic sex chromosome inactivation in mice

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The methyltransferase Setdb1 is essential for meiosis and mitosis in mouse oocytes and early embryo

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