EPIGENETIC MECHANISMS IN TRANSCRIPTIONAL CONTROL
In every eukaryotic cell the genome is packaged into chromatin which is mainly composed of the DNA and histone proteins. The organization and structure of chromatin within the nucleus can regulate the transcription of DNA. Post-translational modifications placed on histone proteins, such as methylation, acetylation and phosphorylation, can influence the configuration of chromatin and ultimately control DNA accessibility by the transcriptional machinery. Therefore, histone modifying enzymes and their underlying modifications play a crucial role in the regulation of gene expression. Of particular interest to our research group are the enzymes that methylate arginine residues on histone proteins known as protein arginine methyltransferases (PRMTs) and N-terminal transferases (NTTs) that modify the N-alpha-terminal ends of histones. Our previous work has begun to unravel the molecular mechanisms by which these histone modifying enzymes and their associated modifications control gene expression. Specifically, we have shown that histone H4 N-alpha-terminal acetylation mediated by NAA40 prevents the deposition of an adjacent PRMT-mediated histone H4 arginine 3 methylation mark to activate transcription at specific sets of genes.