马克斯·普朗克免疫生物学和表观遗传学研究所Asifa Akhtar团队取得一项新突破。他们的最新研究探明了组蛋白乙酰化依赖性BRD2聚类指导转录动力学。2026年4月9日，国际知名学术期刊《自然—遗传学》发表了这一成果。

在单主题胚胎干细胞中，该课题组人员发现BRD2通过与TFIID的相互作用在维持启动子上Pol II的募集中发挥了重要作用，这在暂停释放受损的情况下变得尤为重要。结合快速蛋白质降解，化学基因组学和超分辨率显微镜，该课题组发现MOF介导的组蛋白H4乙酰化促进BRD2染色质关联，从而使BRD2细胞聚集。因此，BRD2内在无序区域的MOF缺失或缺失在很大程度上概括了BRD2缺失时观察到的启动子富集和转录机制的聚集缺陷。因此，这些发现支持了一种模型，即组蛋白乙酰化依赖的BRD2时空动力学协调转录机制来调节转录起始。

据悉，溴域（BD）和外端结构域（BET）蛋白是RNA聚合酶II （Pol II）介导的转录的关键调控因子，它们的BDs是有希望的药物靶点。然而，组蛋白乙酰化和单个BET蛋白的染色质动力学之间的相互作用在转录调节方面尚未完全了解。

附：英文原文

Title: Histone acetylation-dependent clustering of BRD2 instructs transcription dynamics

Author: Erdogdu, Niyazi Umut, Guhathakurta, Sukanya, Oellers, Ronald, Shvedunova, Maria, Morin, Jose A., Patrick, Eric M., Seyfferth, Janine, Deboutte, Ward, Gomez-Auli, Alejandro, Mittler, Gerhard, Ciss, Ibrahim I., Akhtar, Asifa

Issue&Volume: 2026-04-09

Abstract: Bromodomain (BD) and extra-terminal domain (BET) proteins are key regulators of RNA polymerase II (Pol II)-mediated transcription and their BDs represent promising drug targets. Yet, the interplay between histone acetylation and the chromatin dynamics of individual BET proteins with respect to transcriptional regulation is not fully understood. Here in mouse embryonic stem cells, we uncover an essential role of BRD2 in maintaining Pol II recruitment at promoters through its interaction with TFIID, which becomes particularly critical under the conditions of impaired pause release. Combining rapid protein degradation, chemogenomics and super-resolution microscopy, we show that MOF-mediated histone H4 acetylation promotes BRD2 chromatin association, which in turn enables BRD2 clustering. Accordingly, MOF depletion or deletion of the BRD2’s intrinsically disordered region largely recapitulates defects in promoter enrichment and clustering of the transcription machinery observed upon BRD2 loss. Thus, these findings support a model in which histone acetylation-dependent spatiotemporal dynamics of BRD2 coordinate the transcription machinery to regulate transcription initiation.

DOI: 10.1038/s41588-026-02533-x

Source: https://www.nature.com/articles/s41588-026-02533-x