YTHDF1 facilitates PRC1‐mediated H2AK119ub in human ES cells

Author:

Zhang Jingyuan12345,Wang Tianyu12345ORCID,Shi Ruona23,Zhao Yuan14,Zhang Yanqi12345,Zhang Cong12345,Xing Qi12345,Zhou Tiancheng1234,Shan Yongli12345,Yao Hongjie13456ORCID,Zhang Xiaofei1345,Pan Guangjin12345ORCID

Affiliation:

1. CAS Key Laboratory of Regenerative Biology Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China

2. University of Chinese Academy of Sciences Beijing China

3. Centre for Regenerative Medicine and Health Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences Hong Kong SAR China

4. CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Lineage and Development Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China

5. Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences Guangzhou China

6. Department of Basic Science Research Guangzhou Laboratory Guangzhou China

Abstract

AbstractPolycomb repressive complexes (PRCs) play critical roles in cell fate decisions during normal development as well as disease progression through mediating histone modifications such as H3K27me3 and H2AK119ub. How exactly PRCs recruited to chromatin remains to be fully illuminated. Here, we report that YTHDF1, the N6‐methyladenine (m6A) RNA reader that was previously known to be mainly cytoplasmic, associates with RNF2, a PRC1 protein that mediates H2AK119ub in human embryonic stem cells (hESCs). A portion of YTHDF1 localizes in the nuclei and associates with RNF2/H2AK119ub on a subset of gene loci related to neural development functions. Knock‐down YTHDF1 attenuates H2AK119ub modification on these genes and promotes neural differentiation in hESCs. Our findings provide a noncanonical mechanism that YTHDF1 participates in PRC1 functions in hESCs.

Publisher

Wiley

Subject

Cell Biology,Clinical Biochemistry,Physiology

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