关键词: B cell differentiation BRG1 EBF1 IDR chromatin condensates phase separation

Mesh : Cell Lineage / genetics B-Lymphocytes Gene Expression Regulation Transcription Factors / genetics metabolism Heterochromatin / metabolism

来  源:   DOI:10.1101/gad.350828.123   PDF(Pubmed)

Abstract:
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.
摘要:
先锋转录因子EBF1的B谱系引发需要固有无序区域(IDR)的功能。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,并显示染色质结合受损,招募BRG1,并激活特定的靶基因。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。
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