Title: Characterization of histone acylations links chromatin modifications with metabolism.
Authors: Simithy, Johayra; Sidoli, Simone; Yuan, Zuo-Fei; Coradin, Mariel; Bhanu, Natarajan V; Marchione, Dylan M; Klein, Brianna J; Bazilevsky, Gleb A; McCullough, Cheryl E; Magin, Robert S; Kutateladze, Tatiana G; Snyder, Nathaniel W; Marmorstein, Ronen; Garcia, Benjamin A
Published In Nat Commun, (2017 10 26)
Abstract: Over the last decade, numerous histone acyl post-translational modifications (acyl-PTMs) have been discovered, of which the functional significance is still under intense study. Here, we use high-resolution mass spectrometry to accurately quantify eight acyl-PTMs in vivo and after in vitro enzymatic assays. We assess the ability of seven histone acetyltransferases (HATs) to catalyze acylations on histones in vitro using short-chain acyl-CoA donors, proving that they are less efficient towards larger acyl-CoAs. We also observe that acyl-CoAs can acylate histones through non-enzymatic mechanisms. Using integrated metabolomic and proteomic approaches, we achieve high correlation (R 2 > 0.99) between the abundance of acyl-CoAs and their corresponding acyl-PTMs. Moreover, we observe a dose-dependent increase in histone acyl-PTM abundances in response to acyl-CoA supplementation in in nucleo reactions. This study represents a comprehensive profiling of scarcely investigated low-abundance histone marks, revealing that concentrations of acyl-CoAs affect histone acyl-PTM abundances by both enzymatic and non-enzymatic mechanisms.
PubMed ID: 29070843
MeSH Terms: No MeSH terms associated with this publication