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CTCF-mediated 3D chromatin predetermines the gene expression program in the male germline (Hi-C)

ABSTRACT: Spermatogenesis is a unidirectional differentiation process to produce haploid sperm. However, it remains largely unknown how the gene expression program is determined to direct a unidirectional differentiation. Here we unveil the high-resolution 3D chromatin architecture of male germ cells and show that CTCF-mediated 3D chromatin predetermines the gene expression program required for spermatogenesis. At the mitosis-to-meiosis transition, the germline-specific Polycomb protein SCML2 resolves chromatin loops specific to mitotic spermatogonia. On autosomes, CTCF-mediated 3D chromatin manifests the structural feature of meiosis-specific super-enhancer (meiotic SE) loci already in undifferentiated spermatogonia. In meiotic spermatocytes, the master transcription factor A-MYB is recruited to these meiotic SE loci to strengthen their 3D contacts to instruct the burst of meiotic gene expression. Further, SCML2 and A-MYB establish unique 3D chromatin of the sex chromosomes in meiotic sex chromosome inactivation. We propose that CTCF-mediated 3D chromatin underlines epigenetic priming to direct unidirectional differentiation, thereby determining the cellular identity of the male germline.

ORGANISM(S): Mus musculus

PROVIDER: GSE244676 | GEO | 2024/12/13

REPOSITORIES: GEO

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CTCF-mediated 3D chromatin predetermines the gene expression program in the male germline (ChIP-seq)

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