Histone modifications predispose genome regions to breakage and translocation.
Histone modifications predispose genome regions to breakage and translocation.
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DOI：
10.1101/gad.262170.115
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发表时间：
2015-07-01
影响因子：
10.5
通讯作者：
Misteli T
中科院分区：
文献类型：
--
作者：
Burman B;Zhang ZZ;Pegoraro G;Lieb JD;Misteli T
伯曼等人。发现临床相关易位基因组区域中几种组蛋白修饰的富集。组蛋白标记的实验调节使基因组区域对核酸内切酶攻击或辐射的破坏敏感，并促进染色体易位的形成。染色体易位是癌细胞的既定标志，通常发生在基因组中的非随机位点。定义周期性染色体断点的分子特征在很大程度上是未知的。通过结合生物信息学、生化分析和细胞分析，我们确定了特定的组蛋白修饰是染色体断裂和易位的促进剂。我们展示了临床相关易位基因组区域的几种组蛋白修饰的富集。组蛋白标记的实验调节使基因组区域对核酸内切酶攻击或辐射的破坏敏感，并促进内源基因位点染色体易位的形成。我们的结果表明，组蛋白修饰使基因组区域容易发生染色体断裂和易位。
Burman et al. find enrichment of several histone modifications over clinically relevant translocation-prone genome regions. Experimental modulation of histone marks sensitized genome regions to breakage by endonuclease challenge or irradiation and promoted formation of chromosome translocations. Chromosome translocations are well-established hallmarks of cancer cells and often occur at nonrandom sites in the genome. The molecular features that define recurrent chromosome breakpoints are largely unknown. Using a combination of bioinformatics, biochemical analysis, and cell-based assays, we identify here specific histone modifications as facilitators of chromosome breakage and translocations. We show enrichment of several histone modifications over clinically relevant translocation-prone genome regions. Experimental modulation of histone marks sensitizes genome regions to breakage by endonuclease challenge or irradiation and promotes formation of chromosome translocations of endogenous gene loci. Our results demonstrate that histone modifications predispose genome regions to chromosome breakage and translocations.