组蛋白甲基转移酶的研究进展

Progress in the study of histone methyltransferases

组蛋白的甲基化修饰主要是由一类含有SET结构域的蛋白来执行的,组蛋白甲基化修饰参与异染色质形成、基因印记、X染色体失活和转录调控等多种主要生理功能,组蛋白的修饰作用是表观遗传学研究的一个重要领域。组蛋白甲基化的异常与肿瘤发生等多种人类疾病相关,可以特异性地激活或者抑制基因的转录活性。研究发现,组蛋白甲基转移酶的作用对象不仅仅限于组蛋白,某些非组蛋白也可以被组蛋白甲基转移酶甲基化,这将为探明细胞内部基因转录、信号转导、甚至个体的发育和分化机制提供更广阔的空间。

Site- and state-specific lysine methylation of histones is catalyzed by a family of proteins including those contain the evolutionarily conserved SET domain. Research on histone methyltransferases is a part of epigenetics, which plays a fundamental role in heterochromatin formation, X-chromosome inactivation and transcription regulation. Aberrant histone methylation was linked to a number of developmental disorders and human disease including several carcinomas. Histone lysine methylation is a functionally complex process, as it can either activate or repress transcription, depending on sequence-specific lysine methylation site in histones. Non-histone proteins were found to be methylated by SET domain-containing histone methyltransferases whose primary targets were presumed to be histones. The researches on histone methyltransferases will make a completely new space for transcriptional activity, embryonic development, cell differentiation, and signal transduction.