A Non-canonical BCOR-PRC1.1 Complex Represses Differentiation Programs in Human ESCs
收藏干细胞与再生医学数据中心2022-02-20 更新2024-03-06 收录
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Polycomb group proteins regulate self-renewal anddifferentiation in many stem cell systems. Whenassembled into two canonical complexes, PRC1and PRC2, they sequentially deposit H3K27me3and H2AK119ub histone marks and establish repressivechromatin, referred to as Polycomb domains.Non-canonical PRC1 complexes retain RING1/RNF2 E3-ubiquitin ligases but have unique sets ofaccessory subunits. How these non-canonical complexesrecognize and regulate their gene targetsremains poorly understood. Here, we show thatthe BCL6 co-repressor (BCOR), a member of thePRC1.1 complex, is critical for maintaining primedpluripotency in human embryonic stem cells(ESCs). BCOR depletion leads to the erosion ofPolycomb domains at key developmental loci andthe initiation of differentiation along endodermand mesoderm lineages. The C terminus of BCORregulates the assembly and targeting of thePRC1.1 complex, while the N terminus contributesto BCOR-PRC1.1 repressor function. Our findingsadvance understanding of Polycomb targeting andrepression in ESCs and could apply broadly acrossdevelopmental systems.
提供机构:
University of Minnesota
创建时间:
2022-02-20



