关键词: Brg1/Smarca4 EpiSCs MLL3/4 RNAPII SWI/SNF eRNA enhancer mediator (Med1) naive p300/CBP primed

Mesh : Animals Humans Cell Lineage / genetics Chromatin Assembly and Disassembly Chromosomal Proteins, Non-Histone / metabolism genetics DNA Helicases / metabolism genetics Enhancer Elements, Genetic Nuclear Proteins / metabolism genetics Transcription Factors / metabolism genetics

来  源:   DOI:10.1016/j.molcel.2024.03.013   PDF(Pubmed)

Abstract:
RNA transcribed from enhancers, i.e., eRNA, has been suggested to directly activate transcription by recruiting transcription factors and co-activators. Although there have been specific examples of eRNA functioning in this way, it is not clear how general this may be. We find that the AT-hook of SWI/SNF preferentially binds RNA and, as part of the esBAF complex, associates with eRNA transcribed from intronic and intergenic regions. Our data suggest that SWI/SNF is globally recruited in cis by eRNA to cell-type-specific enhancers, representative of two distinct stages that mimic early mammalian development, and not at enhancers that are shared between the two stages. In this manner, SWI/SNF facilitates recruitment and/or activation of MLL3/4, p300/CBP, and Mediator to stage-specific enhancers and super-enhancers that regulate the transcription of metabolic and cell lineage priming-related genes. These findings highlight a connection between ATP-dependent chromatin remodeling and eRNA in cell identity and typical- and super-enhancer activation.
摘要:
从增强子转录的RNA,即,eRNA,已建议通过募集转录因子和共激活剂直接激活转录。尽管已经有这样运作的eRNA的具体例子,目前尚不清楚这可能有多普遍。我们发现SWI/SNF的AT-hook优先结合RNA,作为esBAF综合体的一部分,与从内含子和基因间区域转录的eRNA相关。我们的数据表明,SWI/SNF在全球范围内通过eRNA以顺式招募到细胞类型特异性增强子,代表模拟哺乳动物早期发育的两个不同阶段,而不是在两个阶段之间共享的增强剂。以这种方式,SWI/SNF促进MLL3/4,p300/CBP的招募和/或激活,和调节代谢和细胞谱系启动相关基因转录的阶段特异性增强子和超增强子。这些发现强调了ATP依赖性染色质重塑和eRNA在细胞身份和典型和超增强子激活中的联系。
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