奥地利科学院CeMM分子医学研究中心Stefan Kubicek和Sandra Schick研究组合作取得最新进展。他们表明急性编码BRG1 / BRM相关因子（BAF）扰动会导致染色质可及性即可变化。2021年2月8日出版的《自然-遗传学》杂志发表了这一最新研究成果。
他们使用dTAG系统诱导BAF亚基的急性降解，并证明染色质改变的建立速度快于一个细胞周期的持续时间。使用BAF复合ATPase亚基的药理抑制剂和化学降解剂，他们表明维持基因组可及性需要恒定的ATP依赖性重塑。在旁系同源缺陷的背景下，合成致死亚基的急剧降解会完全废除BAF复杂功能，导致BAF控制位点（特别是在超级增强子处）的染色质可及性几乎完全丧失，从而提供了复杂内部合成致死性的机制。
据悉，BAF染色质重塑复合体的亚基的基因中与癌症相关的功能丧失突变通常会导致严重的染色质可及性变化，特别是在重要的监管区域。然而，仍不清楚如何随时间建立这些变化（例如，立即产生的后果或长期适应），以及它们是否对复合体内合成致死具有推动性，从而消除了BAF复合物的形成或活性。
附：英文原文
Title: Acute BAF perturbation causes immediate changes in chromatin accessibility
Author: Sandra Schick, Sarah Grosche, Katharina Eva Kohl, Danica Drpic, Martin G. Jaeger, Nara C. Marella, Hana Imrichova, Jung-Ming G. Lin, Gerald Hofsttter, Michael Schuster, Andr F. Rendeiro, Anna Koren, Mark Petronczki, Christoph Bock, Andr C. Mller, Georg E. Winter, Stefan Kubicek
Issue&Volume: 2021-02-08
Abstract: Cancer-associated, loss-of-function mutations in genes encoding subunits of the BRG1/BRM-associated factor (BAF) chromatin-remodeling complexes1,2,3,4,5,6,7,8 often cause drastic chromatin accessibility changes, especially in important regulatory regions9,10,11,12,13,14,15,16,17,18,19. However, it remains unknown how these changes are established over time (for example, immediate consequences or long-term adaptations), and whether they are causative for intracomplex synthetic lethalities, abrogating the formation or activity of BAF complexes9,20,21,22,23,24. In the present study, we use the dTAG system to induce acute degradation of BAF subunits and show that chromatin alterations are established faster than the duration of one cell cycle. Using a pharmacological inhibitor and a chemical degrader of the BAF complex ATPase subunits25,26, we show that maintaining genome accessibility requires constant ATP-dependent remodeling. Completely abolishing BAF complex function by acute degradation of a synthetic lethal subunit in a paralog-deficient background results in an almost complete loss of chromatin accessibility at BAF-controlled sites, especially also at superenhancers, providing a mechanism for intracomplex synthetic lethalities.
DOI: 10.1038/s41588-021-00777-3
Source: https://www.nature.com/articles/s41588-021-00777-3
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
官方网址：https://www.nature.com/ng/
投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex
本期文章：《自然—遗传学》：Online/在线发表
