Berger S L
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Cold Spring Harb Symp Quant Biol. 2010;75:23-6. doi: 10.1101/sqb.2010.75.044. Epub 2011 Apr 5.
Regulation of transcription involves a large number of histone lysine and arginine posttranslational modifications found marking gene promoters and gene bodies. Within histones there are abundant accessible serine/threonine/tyrosine residues for potential phosphorylation; however, few sites have been clearly documented with regard to actual modification, relevant physiological pathway, and cognate enzyme. In addition, kinases within signaling pathways are thought to be localized to the cytoplasm and thus not able to directly modify histones within chromatin in the nucleus. However, direct assays in the model eukaryote Saccharomyces cerevisiae via chromatin immunoprecipitation have placed numerous signaling kinases at promoters and within gene bodies. In addition, recent studies in mammalian cells of two signaling pathways place the terminal kinase within the nucleus or directly at genes, have identified histone phosphorylation sites, and furthermore, have uncovered potential mechanisms by which these histone phosphorylation sites activate transcription. These results lead to a gathering appreciation of the potential role of signal transduction kinase-mediated direct histone phosphorylation in regulating transcription.
转录调控涉及大量在基因启动子和基因体上发现的组蛋白赖氨酸和精氨酸的翻译后修饰。在组蛋白中，有大量可及的丝氨酸/苏氨酸/酪氨酸残基可用于潜在的磷酸化；然而，关于实际修饰、相关生理途径和同源酶，鲜有位点得到明确记录。此外，信号通路中的激酶被认为定位于细胞质中，因此无法直接修饰细胞核染色质中的组蛋白。然而，通过染色质免疫沉淀在模式真核生物酿酒酵母中进行的直接检测已将多种信号激酶定位在启动子和基因体内。此外，最近在哺乳动物细胞中对两条信号通路的研究表明，末端激酶位于细胞核内或直接位于基因处，已鉴定出组蛋白磷酸化位点，而且还揭示了这些组蛋白磷酸化位点激活转录的潜在机制。这些结果使人们越来越认识到信号转导激酶介导的直接组蛋白磷酸化在调控转录中的潜在作用。
