粘蛋白
溴尿嘧啶
染色质
生物
分区(防火)
核小体
嘉雅宠物
计算生物学
基因组
遗传学
CTCF公司
细胞生物学
组蛋白
转录因子
DNA
增强子
基因
生物化学
酶
作者
Liangqi Xie,Peng Dong,Yuanming Qi,Tsung Han Hsieh,Brian P. English,Seolkyoung Jung,Xingqi Chen,Margherita De Marzio,Rafael Casellas,Howard Y. Chang,Bin Zhang,Robert Tjian,Zhe Liu
出处
期刊:Nature Genetics
[Springer Nature]
日期:2022-04-01
卷期号:54 (4): 481-491
被引量:27
标识
DOI:10.1038/s41588-022-01044-9
摘要
Mammalian chromosomes are organized into megabase-sized compartments that are further subdivided into topologically associating domains (TADs). While the formation of TADs is dependent on cohesin, the mechanism behind compartmentalization remains enigmatic. Here, we show that the bromodomain and extraterminal (BET) family scaffold protein BRD2 promotes spatial mixing and compartmentalization of active chromatin after cohesin loss. This activity is independent of transcription but requires BRD2 to recognize acetylated targets through its double bromodomain and interact with binding partners with its low-complexity domain. Notably, genome compartmentalization mediated by BRD2 is antagonized on the one hand by cohesin and on the other hand by the BET homolog protein BRD4, both of which inhibit BRD2 binding to chromatin. Polymer simulation of our data supports a BRD2-cohesin interplay model of nuclear topology, in which genome compartmentalization results from a competition between loop extrusion and chromatin-state-specific affinity interactions.
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