Polycomb repressive complex 1 (PRC1) role in skin epithelium development [HF I53A]

Polycomb repressive complexes (PRC) 1 and 2 are essential chromatin regulators of cell identity. PRC1, a dominant executer of Polycomb-mediated control, functions as multiple sub-complexes that possess catalytic-dependent H2AK119 mono-ubiquitination (H2AK119ub) and catalytic-independent activities. Here, we show that despite its well-established repressor functions, PRC1 binds to both silent and active genes. Through in vivo loss-of-function studies, we show that global PRC1 function is essential for skin development and stem cell (SC) specification. Overall design: Newborn mouse epidermal cells were purified from Ring1a-/- Ring1b-/I53A mutants and control mice. RNA from the sorted cells was analyzed by RNA-seq.多梳抑制复合体（Polycomb Repressive Complex, PRC）1与2是调控细胞身份的核心染色质调控因子。PRC1作为多梳介导基因调控的主要执行因子，以多种亚复合体形式发挥功能，兼具依赖催化活性的H2AK119单泛素化（H2AK119ub）活性与非催化依赖活性。尽管其基因沉默功能已被广泛证实，本研究发现PRC1可同时结合沉默基因与活跃转录基因。通过体内功能丧失实验，我们证实全局PRC1功能对于皮肤发育与干细胞（Stem Cell, SC）特化不可或缺。实验整体设计：从Ring1a基因纯合敲除、Ring1b基因携带I53A突变的突变小鼠与对照小鼠中分离纯化新生小鼠表皮细胞，对分选所得细胞的总RNA进行RNA-seq测序分析。