Inhibition of acetyltransferase alters different histone modifications: probed by small molecule inhibitor plumbagin

Abstract

Histone modifications; acetylation, methylation (both Lysine and Arginine) etc., at different positions regulates the chromatin fluidity and function in a combinatorial manner, which could be referred as an epigenetic language. In the context of transcription, histone acetylation, methylation and phosphorylation at specific sites, especially at the N-terminal tails of histones play very important roles in activation and/or repression. While acetylation of histones is generally important for transcriptional activation, methylation and phosphorylation could also be involved in repression, depending on the context. Here, we have investigated the crosstalk of histone modifications on a gross scale over histone H3, using a small molecule inhibitor of lysine acetyltransferase KAT3B/p300, Plumbagin, to analyze the histone modification profile upon inhibition of acetylation. In addition to the inhibition of acetylation, there was a concomitant decrease of transcriptional activation mark, H3 lysine 4 trimethylation (H3K4me3) in the cellular context. The histone H3 Serine 10 Phosphorylation (H3S10p) also decreased upon inhibition of acetylation. However, there were no changes observed with transcriptional repressive marks like H3 Lysine 9 di/trimethylation (H3K9me2/me3) suggesting that transcriptional activation marks were selectively targeted. These data suggest that Plumbagin induces a distinct modification profile involving transcriptional activation marks H3K4me3 and H3S10 phosphorylation in the context of histone acetylation brought about by KAT3B/ p300.