CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, 510530, China.
Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, CAS Center for Excellence in Molecular Cell Science, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.
Nat Commun. 2018 May 15;9(1):1463. 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.
多梳抑制复合物 1（PRC1）是基因表达和发育的重要调节因子。PRC1 包含 E3 连接酶 RING1A/B，其单泛素化组蛋白 H2A 的赖氨酸 119（H2AK119ub1），并根据 PCGF 亚基的存在分为六个主要复合物。在这里，我们报告说，六个 PCGF 旁系同源物之一的 PCGF5 是小鼠胚胎干细胞（mESC）向神经细胞命运分化的重要要求。虽然 PCGF5 对于 mESC 的自我更新不是必需的，但它的缺失通过激活 SMAD2/TGF-β 信号通路来阻止 mESC 的神经分化。PCGF5 功能丧失会损害神经特异性基因周围 H2AK119ub1 和 H3K27me3 的减少，并使它们保持沉默。我们的结果表明，PCGF5 可能既是 SMAD2/TGF-β 信号通路的抑制剂，也是神经分化的促进剂。总之，我们的研究结果揭示了 PCGF5 在指导 PRC1 控制细胞命运方面的关键上下文特异性功能。
