Epigenetic modifications driving ground state pluripotency exit require an NF-κB-independent chromatin IκBα function
bioRxiv (Cold Spring Harbor Laboratory)(2023)
摘要
Summary Inflammatory signals are key in development and cell differentiation but their orchestration with pluripotency and stemness signals is poorly understood. Our previous work identified a chromatin function of IκBα, the NF-κB inhibitor, that is crucial for differentiation in different types of somatic stem cells. Here we demonstrate that deficiency of IκBα imposes a profound chromatin rewiring defect that impacts on DNA methylation, histone post-translational modifications and transcriptional regulation, stabilizing mouse embryonic stem cells (ESCs) in a ground state of pluripotency while preventing them from pluripotency exit and differentiation. By engineering separation-of-function mutants of IκBα with specific binding to either NF-κB or histones, we demonstrate that regulation of pluripotency state by IκBα is independent of NF-κB but requires the chromatin-related IκBα function.
更多查看译文
关键词
epigenetic modifications,ground state pluripotency exit,b-independent
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要