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Enhancer switching in cell lineage priming is linked to eRNA, Brg1’s AT-hook, and SWI/SNF recruitment
Molecular Cell ( IF 16.0 ) Pub Date : 2024-04-08 , DOI: 10.1016/j.molcel.2024.03.013
Dhurjhoti Saha , Srinivas Animireddy , Junwoo Lee , Anna Thommen , McKenzie M. Murvin , Yue Lu , J. Mauro Calabrese , Blaine Bartholomew

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.



中文翻译:

细胞谱系启动中的增强子转换与 eRNA、Brg1 的 AT-hook 和 SWI/SNF 招募有关

由增强子转录的RNA,即eRNA,被认为可以通过招募转录因子和共激活子来直接激活转录。尽管已经有 eRNA 以这种方式发挥作用的具体例子,但尚不清楚这种方式有多普遍。我们发现 SWI/SNF 的 AT 钩优先结合 RNA,并且作为 esBAF 复合物的一部分,与从内含子和基因间区域转录的 eRNA 结合。我们的数据表明,SWI/SNF 被 eRNA 以式方式全局招募到细胞类型特异性增强子,代表模拟早期哺乳动物发育的两个不同阶段,而不是在两个阶段之间共享的增强子处。通过这种方式,SWI/SNF 促进 MLL3/4、p300/CBP 和介体招募和/或激活至阶段特异性增强子和超级增强子,调节代谢和细胞谱系启动相关基因的转录。这些发现强调了 ATP 依赖性染色质重塑与细胞身份和典型增强子和超级增强子激活中的 eRNA 之间的联系。

更新日期:2024-04-08
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