再髓鞘化
PRC2
心理压抑
神经发生
表观遗传学
生物
少突胶质细胞
染色质重塑
细胞生物学
Wnt信号通路
细胞分化
谱系(遗传)
染色质
EZH2型
神经科学
遗传学
基因
基因表达
髓鞘
中枢神经系统
作者
Jiajia Wang,Jiajia Wang,Lijun Yang,Yong-Jie Du,Jincheng Wang,Qinjie Weng,Xuezhao Liu,Elizabeth Nicholson,Mei Xin,Q Richard Lu,Q Richard Lu
标识
DOI:10.1083/jcb.202310143
摘要
Chromatin-remodeling protein BRG1/SMARCA4 is pivotal for establishing oligodendrocyte (OL) lineage identity. However, its functions for oligodendrocyte-precursor cell (OPC) differentiation within the postnatal brain and during remyelination remain elusive. Here, we demonstrate that Brg1 loss profoundly impairs OPC differentiation in the brain with a comparatively lesser effect in the spinal cord. Moreover, BRG1 is critical for OPC remyelination after injury. Integrative transcriptomic/genomic profiling reveals that BRG1 exhibits a dual role by promoting OPC differentiation networks while repressing OL-inhibitory cues and proneuronal programs. Furthermore, we find that BRG1 interacts with EED/PRC2 polycomb-repressive-complexes to enhance H3K27me3-mediated repression at gene loci associated with OL-differentiation inhibition and neurogenesis. Notably, BRG1 depletion decreases H3K27me3 deposition, leading to the upregulation of BMP/WNT signaling and proneurogenic genes, which suppresses OL programs. Thus, our findings reveal a hitherto unexplored spatiotemporal-specific role of BRG1 for OPC differentiation in the developing CNS and underscore a new insight into BRG1/PRC2-mediated epigenetic regulation that promotes and safeguards OL lineage commitment and differentiation.
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