Acetylation-mediated histone H3 accessibility by chromatin modifiers (2024)

Undergraduate: Brett Smith

Faculty Advisor: Brian Strahl
Department: Biochemistry and Biophysics

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The addition of chemical groups (i.e., post-translational modifications) on DNA and histone proteins is a vital biochemical process important for regulating gene expression. One such post translational modification (PTM) is histone N-terminal tail acetylation, which is thought to increase histone tail and DNA availability towards transcriptional and epigenetic machinery. Recently, studies have shown that acetylation and other post translational modifications often regulate gene expression in combination with each other rather than in isolation. Notably, H3 tail acetylation has been linked to increased H3K4 methylation by methyltransferase enzymes MLL1 and MLL4, but it is unknown whether this mechanism can be extended to other H3 methyltransferases. Using in vitro endpoint assays of methyltransferase activity on differentially acetylated nucleosomes, we observed that the methylation activity of H3K36 methyltransferases SETD2 and NSD2 is stimulated by H3K27 acetylation and that the activity of other H3 writers is largely unaffected. Taken together, these results hint towards the presence of acetylation-specific interactions that mediate PTM crosstalk that could uncover a broader mechanism of biophysical gene regulation.