SETDB1 Links the Meiotic DNA Damage Response to Sex Chromosome Silencing in Mice

• DOI: 10.1016/j.devcel.2018.10.004
• Publication Date: 2018-11-01T15:09:00Z
• Authors: Takayuki Hirota; Paul Blakeley; Mahesh N. Sangrithi; Shantha K. Mahade...; Vesela Encheva; Ambrosius P. Snij...; Elias ElInati; Obah A. Ojarikre; Dirk G. de Rooij; Kathy K. Niakan; James M.A. Turner
• Keywords: Synapsis

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