Immediate-early gene regulation by interplay between different post-translational modifications on human histone H3.

In mammalian cells, induction of immediate-early (IE) gene transcription occurs concomitantly with histone H3 phosphorylation on Ser 10 and is catalyzed by mitogen-activated protein kinases (MAPKs). Histone H3 is an evolutionarily conserved protein located in the core of the nucleosome, along with histones H2A, H2B, and H4. The N-terminal tails of histones protrude outside the chromatin structure and are accessible to various enzymes for post-translational modifications (PTM). Phosphorylation, O-GlcNAc modification, and their interplay often induce functional changes, but it is very difficult to monitor dynamic structural and functional changes in vivo. To get started in this complex task, computer-assisted studies are useful to predict the range in which those dynamic structural and functional changes may occur. As an illustration, we propose blocking of phosphorylation by O-GlcNAc modification on Ser 10, which may result in gene silencing in the presence of methylated Lys 9. Thus, alternate phosphorylation and O-GlcNAc modification on Ser 10 in the histone H3 protein may provide an on/off switch to regulate expression of IE genes.

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