近日，美国福瑞德·哈金森癌症研究中心Sandipan Brahma和Steven Henikoff合作发现，BAF染色质重塑因子与RNA聚合酶II和转录因子协同驱逐核小体。这一研究成果于2023年12月4日在线发表在国际学术期刊《自然—遗传学》上。

研究人员采用化学遗传学方法，并结合时间分辨染色质图谱分析，来剖析了小鼠胚胎干细胞中RNA聚合酶II（RNAPII）、BAF（Brahma-associated factor）和DNA序列特异性转录因子之间的相互作用。研究人员发现，BAF能动态地解开并驱逐可及染色质区域的核小体，而RNAPII启动子近端暂停能稳定BAF的染色质占据，并增强BAF的ATP依赖性核小体驱逐。

研究人员发现，尽管RNAPII和BAF对转录活跃的基因组区域和Polycomb抑制的基因组区域都进行了动态探测，但多能性转录因子染色质结合赋予了BAF介导的染色质重塑和核小体驱逐的位点特异性。这项研究为动态作用的染色质因子之间如何通过功能协同调节特异性核小体组织和染色质可及性提供了一个范例。

研究人员表示，染色质可及性是活跃转录的一个标志，需要 ATP 依赖性核小体重塑，这是由BAF等复合物完成的。然而，转录、核小体重塑和染色质可及性之间的机理联系尚不清楚。

附：英文原文

Title: The BAF chromatin remodeler synergizes with RNA polymerase II and transcription factors to evict nucleosomes

Author: Brahma, Sandipan, Henikoff, Steven

Issue&Volume: 2023-12-04

Abstract: Chromatin accessibility is a hallmark of active transcription and entails ATP-dependent nucleosome remodeling, which is carried out by complexes such as Brahma-associated factor (BAF). However, the mechanistic links between transcription, nucleosome remodeling and chromatin accessibility are unclear. Here, we used a chemical–genetic approach coupled with time-resolved chromatin profiling to dissect the interplay between RNA Polymerase II (RNAPII), BAF and DNA-sequence-specific transcription factors in mouse embryonic stem cells. We show that BAF dynamically unwraps and evicts nucleosomes at accessible chromatin regions, while RNAPII promoter-proximal pausing stabilizes BAF chromatin occupancy and enhances ATP-dependent nucleosome eviction by BAF. We find that although RNAPII and BAF dynamically probe both transcriptionally active and Polycomb-repressed genomic regions, pluripotency transcription factor chromatin binding confers locus specificity for productive chromatin remodeling and nucleosome eviction by BAF. Our study suggests a paradigm for how functional synergy between dynamically acting chromatin factors regulates locus-specific nucleosome organization and chromatin accessibility.

DOI: 10.1038/s41588-023-01603-8

Source: https://www.nature.com/articles/s41588-023-01603-8