Cell Signaling and Transcriptional Regulation via Histone Phosphorylation

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.