美国霍华德休斯医学研究所Zhe Liu等研究人员合作发现，BRD2区室化可及性的基因组。这一研究成果于2022年4月11日在线发表在国际学术期刊《自然—遗传学》上。

研究人员发现，BET（bromodomain and extraterminal）家族的支架蛋白BRD2在粘连蛋白缺失后促进活性染色质的空间混合和分隔。这种活动与转录无关，但需要BRD2通过其双bromodomain识别乙酰化的靶标，并与其低复杂性结构域的结合伙伴相互作用。值得注意的是，由BRD2介导的基因组分隔一方面被粘连蛋白拮抗，另一方面被BET同源蛋白BRD4拮抗，两者都抑制BRD2与染色质结合。这些数据的聚合物模拟支持BRD2-粘连蛋白的核拓扑学相互作用模型，其中基因组的分隔是由环状挤压和染色质状态特定的亲和力相互作用之间的竞争造成的。

据介绍，哺乳动物的染色体被组织成兆字节大小的区室，这些区室又被进一步细分为拓扑关联域（TAD）。虽然TAD的形成依赖于粘连蛋白，但区室化背后的机制仍然是神秘的。

附：英文原文

Title: BRD2 compartmentalizes the accessible genome

Author: Xie, Liangqi, Dong, Peng, Qi, Yifeng, Hsieh, Tsung-Han S., English, Brian P., Jung, SeolKyoung, Chen, Xingqi, De Marzio, Margherita, Casellas, Rafael, Chang, Howard Y., Zhang, Bin, Tjian, Robert, Liu, Zhe

Issue&Volume: 2022-04-11

Abstract: 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.

DOI: 10.1038/s41588-022-01044-9

Source: https://www.nature.com/articles/s41588-022-01044-9