PCGF5 is required for neural differentiation of embryonic stem cells

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.

Polycomb/Trithorax Antagonism: Cellular Memory in Stem Cell Fate and Function

“…As another means of influencing alternate cell fates, PRC1 complexes can act to suppress the expression of specific signaling pathways. For instance, the non-canonical PRC1 complex containing PCGF6 acts to facilitate neural differentiation of ESCs by reinforcing the repression of the SMAD2-TGFb signaling pathway that would otherwise favor mesoderm and endoderm fates (Yao et al, 2018). In addition, this same non-canonical PRC1 complex plays a key role in silencing germ cell-specific genes in ESCs (Endoh et al, 2017).…”

Screening for reproductive biomarkers in Bactrian camel via iTRAQ analysis of proteomes

“…In mammals, PCG proteins are key regulatory factors of many developmental genes (Ma, Zhang, Sun, & Cheng, ). PCGF5 is a promoting factor for the SMAD2/TGF‐β signalling pathway and for neural differentiation, with findings reveal a critical context‐specific function for PCGF5 in directing PRC1 to control cell fate (Yao et al, ). Sha et al () analysed the impact of the deletion of PCGF5 specifically in haematopoietic stem and progenitor cells (HSPCs) and found that PRC1 (containing PCGF5) functions as a histone modifier in vivo, but that role in HSPCs is limited and can be compensated by other PRC1‐related complexes in HSPCs.…”

Polycomb group RING finger protein 5 influences several developmental signaling pathways during the in vitro differentiation of mouse embryonic stem cells

“…Previous reports have shown that Pcgf5 is dispensable for mESC self‐renewal by checking cell morphology and expression of core pluripotency markers (Yao et al, 2018; Zhao et al, 2017). In our study, we also did not detect any major morphological changes between Pcgf5 −/− and WT mESCs grown in 2i/L medium.…”