表观遗传学
表观基因组
染色质
生物
组蛋白
组蛋白密码
表观遗传学
组蛋白甲基化
DNA甲基化
遗传学
计算生物学
组蛋白甲基转移酶
染色质重塑
DNA
细胞生物学
核小体
基因
基因表达
作者
Kyung-Min Noh,C. David Allis,Haitao Li
标识
DOI:10.1021/acschembio.5b00830
摘要
Covalent modifications of both DNA and histones act in concert to define the landscape of our epigenome. In this review, we explore the interconnections between histone and DNA modifications by focusing on a conserved chromatin-binding regulatory domain, the ATRX-DNMT3-DNMT3L (ADD) domain. New studies show that the ADD domain is capable of sensing, and therefore integrating, the status of multiple histone modifications. This in turn dictates the in vivo localization or allosteric regulation of the full-length ADD-containing protein and its ability to function in downstream chromatin remodeling events. Strategies to re-engineer the ADD "reader pocket" in the de novo DNA methyltransferase DNMT3A such that it redirects this "writer" to new genomic loci proved useful in understanding important biological downstream consequences of mis-targeting of DNA methylation via altered reading of histone marks. Combined with genome-editing tools, this approach stands as a poof-of-principle and will be broadly applicable to the elucidation of epigenetic networks that have been altered by "reader" mutations, either artificially or as naturally occurs in some human diseases.
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