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The Dm-Myb Oncoprotein Contributes to Insulator Function and Stabilizes Repressive H3K27me3 PcG Domains
Cell Reports ( IF 7.5 ) Pub Date : 2020-03-10 , DOI: 10.1016/j.celrep.2020.02.053
Juan F Santana 1 , Mrutyunjaya Parida 2 , Abby Long 3 , Joshua Wankum 3 , Anthony J Lilienthal 3 , Krishna M Nukala 3 , J Robert Manak 4
Affiliation  

(Dm-) encodes a protein that plays a key role in regulation of mitotic phase genes. Here, we further refine its role in the context of a developing tissue as a potentiator of gene expression required for proper RNA polymerase II (RNA Pol II) function and efficient H3K4 methylation at promoters. In contrast to its role in gene activation, Myb is also required for repression of many genes, although no specific mechanism for this role has been proposed. We now reveal a critical role for Myb in contributing to insulator function, in part by promoting binding of insulator proteins BEAF-32 and CP190 and stabilizing H3K27me3 Polycomb-group (PcG) domains. In the absence of Myb, H3K27me3 is markedly reduced throughout the genome, leading to H3K4me3 spreading and gene derepression. Finally, Myb is enriched at boundaries that demarcate chromatin environments, including chromatin loop anchors. These results reveal functions of Myb that extend beyond transcriptional regulation.

中文翻译:


Dm-Myb 癌蛋白有助于绝缘体功能并稳定抑制性 H3K27me3 PcG 结构域



(Dm-) 编码一种在有丝分裂期基因调节中起关键作用的蛋白质。在这里,我们进一步完善了它在发育组织中作为基因表达增强剂的作用,这些增强剂是适当的 RNA 聚合酶 II (RNA Pol II) 功能和启动子处有效的 H3K4 甲基化所需的。与它在基因激活中的作用相反,Myb 也是许多基因抑制所必需的,尽管尚未提出这种作用的具体机制。我们现在揭示了 Myb 在促进绝缘体功能方面的关键作用,部分是通过促进绝缘体蛋白 BEAF-32 和 CP190 的结合以及稳定 H3K27me3 多梳组 (PcG) 结构域。在 Myb 缺失的情况下,H3K27me3 在整个基因组中显着减少,导致 H3K4me3 扩散和基因去抑制。最后,Myb 在划分染色质环境的边界处富集,包括染色质环锚。这些结果揭示了 Myb 的功能超出了转录调控范围。
更新日期:2020-03-10
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