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Regularly spaced tyrosines in EBF1 mediate BRG1 recruitment and formation of nuclear subdiffractive clusters
Genes & Development ( IF 10.5 ) Pub Date : 2024-01-01 , DOI: 10.1101/gad.350828.123
Nikolay Zolotarev , Yuanting Wang , Manyu Du , Marc Bayer , Anna Grosschedl , Ibrahim Cisse , Rudolf Grosschedl

B lineage priming by pioneer transcription factor EBF1 requires the function of an intrinsically disordered region (IDR). Here, we examine the role of regularly spaced tyrosines in the IDR as potential determinants of IDR function and activity of EBF1. We found that four Y > A mutations in EBF1 reduced the formation of condensates in vitro and subdiffractive clusters in vivo. Notably, Y > A mutant EBF1 was inefficient in promoting B cell differentiation and showed impaired chromatin binding, recruitment of BRG1, and activation of specific target genes. Thus, regularly spaced tyrosines in the IDR contribute to the biophysical and functional properties of EBF1.

中文翻译:

EBF1 中规则间隔的酪氨酸介导 BRG1 募集和核亚衍射簇的形成

先锋转录因子 EBF1 启动 B 谱系需要本质无序区域 (IDR) 的功能。在这里,我们研究了 IDR 中规则间隔的酪氨酸作为 IDR 功能和 EBF1 活性的潜在决定因素的作用。我们发现 EBF1 中的四个 Y > A 突变减少了体外凝聚物和体内亚衍射簇的形成。值得注意的是,Y > A 突变体 EBF1 在促进 B 细胞分化方面效率低下,并且表现出染色质结合、BRG1 募集和特定靶基因激活受损。因此,IDR 中规则间隔的酪氨酸有助于 EBF1 的生物物理和功能特性。
更新日期:2024-01-01
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