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组蛋白乙酰化动态调节染色质构象和致癌基因等位基因间的特异性相互作用
2021-05-13 15:19

瑞士实验癌症研究所Elisa Oricchio研究组在研究中取得进展。他们的研究发现组蛋白乙酰化动态调节染色质构象和致癌基因等位基因间的特异性相互作用。相关论文发表在2021年5月10日出版的《自然-遗传学》杂志上。

在本研究中,通过比较正常和淋巴瘤B细胞中染色质结构和组蛋白H3赖氨酸27乙酰化(H3K27ac)水平,研究人员发现随H3K27ac局部丰度的不同,增强子与启动子间的相互作用呈现不同的构象。利用遗传或药物降低H3K27ac的水平减弱了这些相互作用的频率和传播,从而改变了癌基因的表达。

此外,由染色体易位介导的增强子劫持影响断点侧翼区域的表观遗传状态,促使在两个同源染色体中形成独特的染色体内相互作用。这些相互作用随等位基因特异性基因表达的变化而改变。总的来说,该工作表明H3K27ac动力学调节调控区域增强子与启动子间相互作用的频率,并可能诱导等位基因特异性染色质构型从而维持癌基因的表达。

据介绍,在癌细胞中,由染色体改变和/或H3K27ac富集增加介导的增强子劫持可以促进癌基因表达。但是,尚不清楚这些事件对增强子-启动子相互作用染色质构象的影响。

附:英文原文

Title: Histone acetylation dynamics modulates chromatin conformation and allele-specific interactions at oncogenic loci

Author: Stephanie Sungalee, Yuanlong Liu, Ruxandra A. Lambuta, Natalya Katanayeva, Maria Donaldson Collier, Daniele Tavernari, Sandrine Roulland, Giovanni Ciriello, Elisa Oricchio

Issue&Volume: 2021-05-10

Abstract: In cancer cells, enhancer hijacking mediated by chromosomal alterations and/or increased deposition of acetylated histone H3 lysine 27 (H3K27ac) can support oncogene expression. However, how the chromatin conformation of enhancer–promoter interactions is affected by these events is unclear. In the present study, by comparing chromatin structure and H3K27ac levels in normal and lymphoma B cells, we show that enhancer–promoter-interacting regions assume different conformations according to the local abundance of H3K27ac. Genetic or pharmacological depletion of H3K27ac decreases the frequency and the spreading of these interactions, altering oncogene expression. Moreover, enhancer hijacking mediated by chromosomal translocations influences the epigenetic status of the regions flanking the breakpoint, prompting the formation of distinct intrachromosomal interactions in the two homologous chromosomes. These interactions are accompanied by allele-specific gene expression changes. Overall, our work indicates that H3K27ac dynamics modulates interaction frequency between regulatory regions and can lead to allele-specific chromatin configurations to sustain oncogene expression.

DOI: 10.1038/s41588-021-00842-x

Source: https://www.nature.com/articles/s41588-021-00842-x

Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:41.307
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex


本期文章:《自然—遗传学》:Online/在线发表

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