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

Yanjiang Liu, Gongcheng Hu, Shengxiong Yang, Mingze Yao, Zicong Liu, Chenghong Yan, Yulin Wen, Wangfang Ping, Juehan Wang, Yawei Song, Xiaotao Dong, Guangjin Pan and Hongjie Yao ()
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Yanjiang Liu: Guangzhou Medical University
Gongcheng Hu: Guangzhou National Laboratory
Shengxiong Yang: Guangzhou Medical University
Mingze Yao: Guangzhou Medical University
Zicong Liu: Guangzhou Medical University
Chenghong Yan: Guangzhou Medical University
Yulin Wen: Guangzhou Medical University
Wangfang Ping: Guangzhou Medical University
Juehan Wang: Guangzhou Medical University
Yawei Song: Guangzhou Medical University
Xiaotao Dong: Guangzhou Medical University
Guangjin Pan: Guangzhou Medical University
Hongjie Yao: Guangzhou Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-42507-9

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