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bioRxiv · 10.1101/2023.11.30.569508

CTCF-mediated 3D chromatin predetermines the gene expression program in the male germline

Kitamura, Y.·Takahashi, K.·Maezawa, S.·Munakata, Y.·Sakashita, A.·Kaplan, N.·Namekawa, S. H.
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Abstract

Spermatogenesis is a unidirectional differentiation process that generates haploid sperm, but how the gene expression program that directs this process is established is largely unknown. Here we determine the high-resolution 3D chromatin architecture of male germ cells during spermatogenesis and show that CTCF-mediated 3D chromatin predetermines the gene expression program required for spermatogenesis. In undifferentiated spermatogonia, CTCF-mediated chromatin contacts on autosomes pre-establish meiosis-specific super-enhancers (SE). These meiotic SE recruit the master transcription factor A-MYB in meiotic spermatocytes, which strengthens their 3D contacts and instructs a burst of meiotic gene expression. We also find that at the mitosis-to-meiosis transition, the germline-specific Polycomb protein SCML2 resolves chromatin loops that are specific to mitotic spermatogonia. Moreover, SCML2 and A-MYB establish the unique 3D chromatin organization of sex chromosomes during meiotic sex chromosome inactivation. We propose that CTCF-mediated 3D chromatin organization enforces epigenetic priming that directs unidirectional differentiation, thereby determining the cellular identity of the male germline.

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Kitamura, Y., Takahashi, K., Maezawa, S., Munakata, Y., Sakashita, A., Kaplan, N., Namekawa, S. H.. 2023-12-02. CTCF-mediated 3D chromatin predetermines the gene expression program in the male germline. https://doi.org/10.1101/2023.11.30.569508

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