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The mitotic STAG3-cohesin defines male germline nucleome

ABSTRACT: Cohesin is a tetrameric protein complex with a ring-like structure that entraps DNA to ensure sister chromatid cohesion and higher-order chromatin organization. The mechanism by which cohesin regulates chromatin structure and gene expression remains a fundamental question. In multicellular organisms, germ cells are unique in that they tailor chromatin organization toward generating totipotency. As part of this program, spermatogonial stem cells (SSCs) in mammals, the source for male gametes, acquire distinctive chromatin organization with exceptionally weak insulation, but the underlying mechanism is unknown. Here, we show that STAG3, exclusively known to form meiotic cohesins, contributes to a mitotic cohesin defining nucleome programming during male germline development. With slower loop extrusion and shorter chromatin residence, STAG3–cohesin attenuates topologically associating domains (TADs) demarcated by CCCTC-binding factor (CTCF), re-wires both enhancer–promoter and Polycomb-mediated repressive interactions, and creates finer and strengthened compartments, establishing a characteristic SSC nucleome. Moreover, STAG3–cohesin controls the balance between SSC self-renewal and differentiation for spermatogenesis. Notably, mitotic STAG3–cohesin is also highly expressed in human B cells and potentially involved in B-cell malignancies. Thus, mitotic STAG3–cohesin with its unique loop extrusion property elucidates a principle for male germline nucleome programming and, more broadly, may contribute to human malignancy.

ORGANISM(S): Homo Sapiens (human) Mus Musculus (mouse)

SUBMITTER: Mitinori Saitou

PROVIDER: PXD045854 | JPOST Repository | Mon Jul 07 00:00:00 BST 2025

REPOSITORIES: jPOST

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			Action	DRS
	220524ko05Sample3.raw	Raw
	220524ko06Sample4.raw	Raw
	220524ko08Sample5.raw	Raw
	220524ko09Sample6.raw	Raw
	220524ko11Sample7.raw	Raw

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