PCGF5 is required for neural differentiation of embryonic stem cells

• Published in: Nature communications Vol. 9; no. 1; pp. 1463 - 12
• Main Authors: Yao, Mingze, Zhou, Xueke, Zhou, Jiajian, Gong, Shixin, Hu, Gongcheng, Li, Jiao, Huang, Kaimeng, Lai, Ping, Shi, Guang, Hutchins, Andrew P., Sun, Hao, Wang, Huating, Yao, Hongjie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.05.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/100; 13/31; 38/15; 38/23; 42/41; 49/39; 49/91; 631/208/176/2016; 631/337/100/2285; 631/532/2117; 64/60; Animals; Cell Differentiation - genetics; Cell Differentiation - physiology; Cell fate; Cell Line; Cell self-renewal; Differentiation; Embryo cells; Embryos; Gene expression; Gene Expression Regulation, Developmental; Gene Knockout Techniques; Histone H2A; Histones - metabolism; Humanities and Social Sciences; Humans; Lysine; Mice; Mouse Embryonic Stem Cells - cytology; Mouse Embryonic Stem Cells - metabolism; multidisciplinary; Neural Stem Cells - cytology; Neural Stem Cells - metabolism; Neurogenesis - genetics; Neurogenesis - physiology; Polycomb group proteins; Polycomb Repressive Complex 1 - metabolism; Polycomb-Group Proteins - deficiency; Polycomb-Group Proteins - genetics; Polycomb-Group Proteins - metabolism; Science; Science (multidisciplinary); Signal Transduction; Signaling; Smad2 protein; Smad2 Protein - metabolism; Stem cell transplantation; Stem cells; Transforming Growth Factor beta - metabolism; Ubiquitin-Protein Ligases - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-03781-0

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. Polycomb-group proteins are key regulators of transcriptional programs that maintain cell identity. Here the authors provide evidence that PCGF5, a subunit of Polycomb Repressor Complex 1, is important for the differentiation of mouse embryonic stem cells towards a neural cell fate.