ArticleGenes & development2024
ATF7IP2/MCAF2 directs H3K9 methylation and meiotic gene regulation in the male germline.
Article in Genes & development, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 8 citations in OpenAlex.
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- MEIOSIN retains a STRA8-independent activity that contributes to meiotic gene activation across vertebrates.Genes & development · 2026Article
- DAXX directs dual modes of H3.4-to-H3.3 histone replacement in the male germline.Genes & development · 2026Article
- Paternal folate deficiency reveals meiosis as a metabolic sensing window in the male germline.bioRxiv : the preprint server for biology · 2026Article
- The Many Faces of SetDB1.Epigenomes · 2026Review
- A multi-omics framework integrating gut microbiota, blood metabolites, and immune cells to elucidate the pathogenesis of Alzheimer's disease.Frontiers in immunology · 2026Article
- Stage-dependent dual mechanisms of MORC2 in retrotransposon silencing and sex chromosome inactivation in germ cells.Nucleic acids research · 2025Article
- Compensation for X-linked Pdha1 silencing by Pdha2 is essential for meiotic double-strand break repair in spermatogenesis.Development (Cambridge, England) · 2025Article
- KRAB zinc-finger proteins regulate endogenous retroviruses to sculpt germline transcriptomes and genome evolution.Genome research · 2025Article
- Epigenetic priming in the male germline.Current opinion in genetics & development · 2024Review
- Recent advances in mechanisms ensuring the pairing, synapsis and segregation of XY chromosomes in mice and humans.Cellular and molecular life sciences : CMLS · 2024Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
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Abstract
H3K9 trimethylation (H3K9me3) plays emerging roles in gene regulation, beyond its accumulation on pericentric constitutive heterochromatin. It remains a mystery why and how H3K9me3 undergoes dynamic regulation in male meiosis. Here, we identify a novel, critical regulator of H3K9 methylation and spermatogenic heterochromatin organization: the germline-specific protein ATF7IP2 (MCAF2). We show that in male meiosis, ATF7IP2 amasses on autosomal and X-pericentric heterochromatin, spreads through the entirety of the sex chromosomes, and accumulates on thousands of autosomal promoters and retrotransposon loci. On the sex chromosomes, which undergo meiotic sex chromosome inactivation (MSCI), the DNA damage response pathway recruits ATF7IP2 to X-pericentric heterochromatin, where it facilitates the recruitment of SETDB1, a histone methyltransferase that catalyzes H3K9me3. In the absence of ATF7IP2, male germ cells are arrested in meiotic prophase I. Analyses of ATF7IP2-deficient meiosis reveal the protein's essential roles in the maintenance of MSCI, suppression of retrotransposons, and global up-regulation of autosomal genes. We propose that ATF7IP2 is a downstream effector of the DDR pathway in meiosis that coordinates the organization of heterochromatin and gene regulation through the spatial regulation of SETDB1-mediated H3K9me3 deposition.
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