YTHDF1 facilitates PRC1-mediated H2AK119ub in human ES cells

J Cell Physiol. 2024 Jan;239(1):152-165. doi: 10.1002/jcp.31152. Epub 2023 Nov 22.

Abstract

Polycomb 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 (m6 A) 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.

Keywords: PRC1; YTHDF1; hESCs; neural development.

MeSH terms

  • Cell Cycle Proteins* / genetics
  • Cell Cycle Proteins* / metabolism
  • Chromatin
  • Histones / genetics
  • Histones / metabolism
  • Human Embryonic Stem Cells* / metabolism
  • Humans
  • Polycomb Repressive Complex 1 / genetics
  • Polycomb Repressive Complex 1 / metabolism
  • Polycomb-Group Proteins / genetics
  • Polycomb-Group Proteins / metabolism
  • Protein Processing, Post-Translational
  • RNA-Binding Proteins* / genetics
  • RNA-Binding Proteins* / metabolism

Substances

  • Cell Cycle Proteins
  • Chromatin
  • Polycomb Repressive Complex 1
  • Polycomb-Group Proteins
  • PRC1 protein, human
  • RNA-Binding Proteins
  • RNF2 protein, human
  • YTHDF1 protein, human
  • Histones