Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells

Polycomb repressive complex 1 (PRC1) comprises two different complexes: CBX-containing canonical PRC1 (cPRC1) and RYBP/YAF2-containing variant PRC1 (vPRC1). RYBP-vPRC1 or YAF2-vPRC1 catalyzes H2AK119ub through a positive-feedback model; however, whether RYBP and YAF2 have different regulatory functi...

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Published in:Nature communications 2023-11, Vol.14 (1), p.7164-7164, Article 7164
Main Authors: Liu, Yanjiang, Hu, Gongcheng, Yang, Shengxiong, Yao, Mingze, Liu, Zicong, Yan, Chenghong, Wen, Yulin, Ping, Wangfang, Wang, Juehan, Song, Yawei, Dong, Xiaotao, Pan, Guangjin, Yao, Hongjie
Format: Article
Language:English
Subjects:
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Antibodies
Cell cycle
Cell differentiation
Efficiency
Embryo cells
Experiments
Humanities and Social Sciences
multidisciplinary
Neural stem cells
Proteins
Science
Science (multidisciplinary)
Stem cells
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Summary:Polycomb repressive complex 1 (PRC1) comprises two different complexes: CBX-containing canonical PRC1 (cPRC1) and RYBP/YAF2-containing variant PRC1 (vPRC1). RYBP-vPRC1 or YAF2-vPRC1 catalyzes H2AK119ub through a positive-feedback model; however, whether RYBP and YAF2 have different regulatory functions is still unclear. Here, we show that the expression of RYBP and YAF2 decreases and increases, respectively, during neural differentiation of embryonic stem cells (ESCs). Rybp knockout impairs neural differentiation by activating Wnt signaling and derepressing nonneuroectoderm-associated genes. However, Yaf2 knockout promotes neural differentiation and leads to redistribution of RYBP binding, increases enrichment of RYBP and H2AK119ub on the RYBP-YAF2 cotargeted genes, and prevents ectopic derepression of nonneuroectoderm-associated genes in neural-differentiated cells. Taken together, this study reveals that RYBP and YAF2 function differentially in regulating mESC neural differentiation. RYBP and YAF2 are a pair of paralog subunits of variant PRC1. Here, authors show that RYBP decrease but YAF2 increase during mESC neural differentiation, and that they are not redundant but function differentially in regulating this differentiation.
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-023-42507-9