INVESTIGATION OF N-METHYL BACKBONE ALTERATIONS IN HUMAN HISTONE 4 BY CATALYSIS OF PCAF ENZYME

Modifications can occur at different levels and time points during the biochemical process of gene expression, from DNA to the final peptide product. One of the most significant posttranslational modifications (PTMs) takes place in histone tails, which arespecial proteins that play a key role in the packaging and organisation of DNA, which means that can regulate indeed the state of chromatin, thereby influencing gene expression and regulation. This regulatory framework underlies the concept of epigenetics. Among the diverse histone modifications, methylation and acetylation of amino acid residues have attracted significant attention in recent years. Most studies have focused on modifications of amino acid side chains due to their accessibility and wellcharacterized three-dimensional properties. However, modifications affecting the peptide backbone have emerged as an additional layer of regulation and are becoming increasingly relevant. This study focuses on the enzyme PCAF (p300/CBP-associated factor), which is a specific histone lysine acetyltransferase (KAT) in charge of incorporating acetyl groups to the side chain of lysine residues. The aim of this project is to investigate whether theincorporation of a methyl group into the peptide backbone of human histone H4 (residues 1–16) influences the catalytic activity of PCAF, and whether this effect is dependent on the position of the modification within the histone sequence.