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Journal article
Characterization of histone acylations links chromatin modifications with metabolism
Nature communications, v 8(1), 1141
26 Oct 2017
PMID: 29070843
Featured in Collection : UN Sustainable Development Goals @ Drexel
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
> 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.
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Details
- Title
- Characterization of histone acylations links chromatin modifications with metabolism
- Creators
- Johayra Simithy - University of PennsylvaniaSimone Sidoli - University of PennsylvaniaZuo-Fei Yuan - University of PennsylvaniaMariel Coradin - University of PennsylvaniaNatarajan V Bhanu - University of PennsylvaniaDylan M Marchione - Translational TherapeuticsBrianna J Klein - University of Colorado DenverGleb A Bazilevsky - University of PennsylvaniaCheryl E McCullough - University of PennsylvaniaRobert S Magin - University of PennsylvaniaTatiana G Kutateladze - University of Colorado DenverNathaniel W Snyder - Drexel UniversityRonen Marmorstein - University of PennsylvaniaBenjamin A Garcia - University of Pennsylvania
- Publication Details
- Nature communications, v 8(1), 1141
- Publisher
- Springer Nature
- Grant note
- R01 GM060293 / NIGMS NIH HHS R35 GM118090 / NIGMS NIH HHS P01 CA196539 / NCI NIH HHS T32 GM008275 / NIGMS NIH HHS P30 ES013508 / NIEHS NIH HHS R01 GM110174 / NIGMS NIH HHS R21 HD087866 / NICHD NIH HHS R01 GM100907 / NIGMS NIH HHS R03 CA211820 / NCI NIH HHS R01 GM101664 / NIGMS NIH HHS R01 AI118891 / NIAID NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- A.J. Drexel Autism Institute
- Web of Science ID
- WOS:000413830800003
- Scopus ID
- 2-s2.0-85032281711
- Other Identifier
- 991019167869604721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology