Torres Idelisse Ortiz, Fujimori Danica Galonić
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Chemistry and Chemical Biology Graduate Program, University of California, San Francisco, CA 94158, USA.
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA; Department of Pharmaceutical Chemistry, University of California, San Francisco, CA 94158, USA.
Curr Opin Struct Biol. 2015 Dec;35:68-75. doi: 10.1016/j.sbi.2015.09.007. Epub 2015 Nov 9.
DNA and histone lysine methylation are dynamic chemical modifications that play a crucial role in the establishment of gene expression patterns during development. Both types of genomic methylation patterns are enzymatically regulated by the opposing activities of enzymes that introduce and remove these marks, known as methylation 'writers' and 'erasers', respectively. The appropriate localization and activity of these enzymes on chromatin is, in part, regulated by chromatin 'readers', protein modules that recognize histone and DNA modifications. Such reading modules are either encoded within the same polypeptide as the catalytic domains of writers and erasers, or present in protein partners that associate with them. Here, we review recent structural, biochemical and biological studies that demonstrate that there are multiple mechanisms by which reader domains can regulate the writers and erasers of histone and DNA methylation.
DNA和组蛋白赖氨酸甲基化是动态化学修饰,在发育过程中基因表达模式的建立中起关键作用。这两种基因组甲基化模式均由分别引入和去除这些标记的酶的相反活性进行酶促调节,这些酶分别称为甲基化“写入器”和“擦除器”。这些酶在染色质上的适当定位和活性部分受染色质“读取器”调节,染色质“读取器”是识别组蛋白和DNA修饰的蛋白质模块。此类读取模块要么与写入器和擦除器的催化域编码在同一多肽中,要么存在于与其相关联的蛋白质伴侣中。在此,我们综述了近期的结构、生化和生物学研究,这些研究表明读取域可通过多种机制调节组蛋白和DNA甲基化的写入器和擦除器。