Year: 2017
Type: article
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 (R2 > 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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: Pennsylvania Department of Health, University of Pennsylvania, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Institute of Environmental Health Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1033967322, G105882222, G1375395185, G1564983540, Structural biology & molecular biophysics training program, G2378792978, G2476700337, Role of Histone and Histone-like Mutations in the Oncogenesis of Human Cancers, G3446286699, G408573313, G5314268435, Lipidomics of meconium in neurodevelopment, Molecular mechanism of chromatin targeting by BRPF1, The influence of prenatal maternal exposures on fetal sterol metabolomics, G9000024894, G9000033147, G9000050642, G9000066551, G9000076191, G9000107195, G9000145318, G9000181507, G9000310355, G9000354559, Center of Excellence in Environmental Toxicology
OpenAlex ID: W2766769418