小柯机器人

2021年2月8日出版的《自然-遗传学》杂志发表了瑞士巴塞尔大学Dirk Schübeler课题组的研究，他们发现哺乳动物SWI/SNF不断恢复染色质的局部可及性。

在本研究中，研究人员使用靶向小鼠SWI/SNF重塑复合物催化亚基的小分子抑制剂发现染色质可及性和转录因子（TF）结合位点处核小体的移除依赖于核小体重塑复合物的持续活性。在重构剂抑制的几分钟内，染色质可及性和TF结合减少。尽管这与TF功能无关，但研究发现与抑制性TF REST相比，激活性TF OCT4（POU5F1）表现出更快的响应。

移除抑制剂后，染色质可及性、核小体移除和基因表达迅速恢复，这表明染色质可及性以细胞自调控的方式连续不断地发生。研究人员猜测TF与染色质结合以及重塑复合物介导的核小体去除并不能代表稳定的情况，而染色质可及性则反映了持续更新过程中动态过程的平衡。

据悉，染色质可及性是转录调控的标志，TF结合和核小体重组介导了染色质可及性。但是，尚不清楚该过程的动态性。

附：英文原文

Title: Mammalian SWI/SNF continuously restores local accessibility to chromatin

Author: Mario Iurlaro, Michael B. Stadler, Francesca Masoni, Zainab Jagani, Giorgio G. Galli, Dirk Schbeler

Issue&Volume: 2021-02-08

Abstract: Chromatin accessibility is a hallmark of regulatory regions, entails transcription factor (TF) binding and requires nucleosomal reorganization. However, it remains unclear how dynamic this process is. In the present study, we use small-molecule inhibition of the catalytic subunit of the mouse SWI/SNF remodeler complex to show that accessibility and reduced nucleosome presence at TF-binding sites rely on persistent activity of nucleosome remodelers. Within minutes of remodeler inhibition, accessibility and TF binding decrease. Although this is irrespective of TF function, we show that the activating TF OCT4 (POU5F1) exhibits a faster response than the repressive TF REST. Accessibility, nucleosome depletion and gene expression are rapidly restored on inhibitor removal, suggesting that accessible chromatin is regenerated continuously and in a largely cell-autonomous fashion. We postulate that TF binding to chromatin and remodeler-mediated nucleosomal removal do not represent a stable situation, but instead accessible chromatin reflects an average of a dynamic process under continued renewal. Chemical inhibition of the SWI/SNF remodeling complex shows decreased accessibility and transcription factor binding within minutes. These changes are rapidly restored on inhibitor removal suggesting that accessible chromatin is regenerated continuously.

DOI: 10.1038/s41588-020-00768-w

Source: https://www.nature.com/articles/s41588-020-00768-w

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex