德国马克斯·普朗克免疫生物学和表观遗传学研究所Rudolf Grosschedl团队在研究中取得进展。他们发现转录因子EBF1中的Prion样结构域促进相分离并使祖细胞染色质向B细胞的编程。该项研究成果发表在2020年11月6日的《免疫》杂志上。

他们研究了C末端结构域（CTD）启用此先导功能的机制。EBF1的CTD可用于最初的染色质靶向，但可通过募集染色质重塑子Brg1来稳定占据。他们发现CTD带有一个prion样结构域（PLD），具有液相-液相分离的能力，并通过EBF1与RNA结合蛋白FUS的相互作用而增强。

Brg1也被包裹进FUS凝聚物并与pro-B细胞中的EBF1和FUS共定位。异源PLD赋予EBF1ΔCTD先导功能。因此，EBF1的相分离能力促进了Brg1介导的染色质的开放和先天祖细胞染色质向B谱系定型染色质的过渡。

据了解，B谱系特异性基因表达的建立需要转录因子与祖细胞的染色质分离。在检测染色质可及性之前，转录因子EBF1可以结合基因组区域，其方式依赖于EBF1的CTD，而与共转录因子无关。

附：英文原文

Title: A Prion-like Domain in Transcription Factor EBF1 Promotes Phase Separation and Enables B Cell Programming of Progenitor Chromatin

Author: Yuanting Wang, Nikolay Zolotarev, Cheng-Yuan Yang, Angelika Rambold, Gerhard Mittler, Rudolf Grosschedl

Issue&Volume: 2020-11-06

Abstract: Establishment of B-lineage-specific gene expression requires the binding of transcriptionfactors to inaccessible chromatin of progenitors. The transcription factor EBF1 canbind genomic regions prior to the detection of chromatin accessibility in a mannerdependent on EBF1’s C-terminal domain (CTD) and independent of cooperating transcriptionfactors. Here, we studied the mechanism whereby the CTD enables this pioneering function.The CTD of EBF1 was dispensable for initial chromatin targeting but stabilized occupancyvia recruitment of the chromatin remodeler Brg1. We found that the CTD harbors a prion-likedomain (PLD) with an ability of liquid-liquid phase separation, which was enhancedby interaction of EBF1 with the RNA-binding protein FUS. Brg1 also partitioned intophase-separated FUS condensates and coincided with EBF1 and FUS foci in pro-B cells.Heterologous PLDs conferred pioneering function on EBF1ΔCTD. Thus, the phase separationability of EBF1 facilitates Brg1-mediated chromatin opening and the transition ofnaive progenitor chromatin to B-lineage-committed chromatin.

DOI: 10.1016/j.immuni.2020.10.009

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30450-7