PCGF5 is required for neural differentiation of embryonic stem cells

Nature Communications
Mingze YaoHongjie Yao

Abstract

Polycomb repressive complex 1 (PRC1) is an important regulator of gene expression and development. PRC1 contains the E3 ligases RING1A/B, which monoubiquitinate lysine 119 at histone H2A (H2AK119ub1), and has been sub-classified into six major complexes based on the presence of a PCGF subunit. Here, we report that PCGF5, one of six PCGF paralogs, is an important requirement in the differentiation of mouse embryonic stem cells (mESCs) towards a neural cell fate. Although PCGF5 is not required for mESC self-renewal, its loss blocks mESC neural differentiation by activating the SMAD2/TGF-β signaling pathway. PCGF5 loss-of-function impairs the reduction of H2AK119ub1 and H3K27me3 around neural specific genes and keeps them repressed. Our results suggest that PCGF5 might function as both a repressor for SMAD2/TGF-β signaling pathway and a facilitator for neural differentiation. Together, our findings reveal a critical context-specific function for PCGF5 in directing PRC1 to control cell fate.

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Citations

Feb 23, 2019·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Vincent LoubiereGiacomo Cavalli
Oct 15, 2019·Journal of Cellular Physiology·Divya Desai, Prasad Pethe
Nov 2, 2019·Briefings in Functional Genomics·Tomas PachanoAlvaro Rada-Iglesias
Sep 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·James M GahanChristine E Schnitzler
May 15, 2020·Cellular and Molecular Life Sciences : CMLS·Bertille MontibusPhilippe Arnaud
Dec 17, 2019·Reproduction in Domestic Animals = Zuchthygiene·Qi WangXingxu Zhao
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Feb 13, 2021·Frontiers in Cell and Developmental Biology·Xinyue LiAijun Hao
Aug 10, 2019·Current Opinion in Neurobiology·Masafumi TsuboiYukiko Gotoh
Apr 3, 2021·Frontiers in Molecular Biosciences·Lei CaoXudong Wu
Feb 20, 2020·Biochemical and Biophysical Research Communications·Hengli NiuLing Chen
Nov 26, 2021·Journal of Molecular Neuroscience : MN·Pablo Ferreira das ChagasElvis Terci Valera
Jan 13, 2022·Molecular Systems Biology·Rui ShaoSimon J Elsässer

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Datasets Mentioned

BETA
GSE95127
GSE107377

Methods Mentioned

BETA
RNA-seq
co-IP
pull-down
ubiquitination
immunoprecipitation
ChIP
ChIP-seq
PCR

Software Mentioned

homer
R
MACS2
UCSC
samtools
TopHat2
Bowtie2
UCSC genome browser
GSEA
Trimmomatic

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