EBF1 中间隔规则的酪氨酸介导了 BRG1 的招募和核亚衍射簇的形成。

IF 7.5 1区生物学 Q1 CELL BIOLOGY Genes & development Pub Date : 2024-02-13 DOI:10.1101/gad.350828.123

Nikolay Zolotarev, Yuanting Wang, Manyu Du, Marc Bayer, Anna Grosschedl, Ibrahim Cisse, Rudolf Grosschedl

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引用次数: 0

摘要

先驱转录因子 EBF1 的 B 系启动需要一个内在无序区（IDR）的功能。在这里，我们研究了 IDR 中间隔规则的酪氨酸作为 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体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，染色质结合、BRG1 募集和特定靶基因的激活均受到损害。因此，IDR中间隔规则的酪氨酸有助于EBF1的生物物理和功能特性。

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Regularly spaced tyrosines in EBF1 mediate BRG1 recruitment and formation of nuclear subdiffractive clusters.

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.

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来源期刊

Genes & development 生物-发育生物学

CiteScore

17.50

自引率

1.90%

发文量

审稿时长

3-6 weeks

期刊介绍： Genes & Development is a research journal published in association with The Genetics Society. It publishes high-quality research papers in the areas of molecular biology, molecular genetics, and related fields. The journal features various research formats including Research papers, short Research Communications, and Resource/Methodology papers. Genes & Development has gained recognition and is considered as one of the Top Five Research Journals in the field of Molecular Biology and Genetics. It has an impressive Impact Factor of 12.89. The journal is ranked #2 among Developmental Biology research journals, #5 in Genetics and Heredity, and is among the Top 20 in Cell Biology (according to ISI Journal Citation Reports®, 2021).