TY - JOUR
T1 - Characterization of histone acylations links chromatin modifications with metabolism
AU - Simithy, Johayra
AU - Sidoli, Simone
AU - Yuan, Zuo Fei
AU - Coradin, Mariel
AU - Bhanu, Natarajan V.
AU - Marchione, Dylan M.
AU - Klein, Brianna J.
AU - Bazilevsky, Gleb A.
AU - McCullough, Cheryl E.
AU - Magin, Robert S.
AU - Kutateladze, Tatiana G.
AU - Snyder, Nathaniel W.
AU - Marmorstein, Ronen
AU - Garcia, Benjamin A.
N1 - Funding Information:
We gratefully acknowledge Dr. Ben Black from the University of Pennsylvania for supplying the recombinant histones and Dr. Andrew Andrews from Fox Chase Cancer Center for supplying the recombinant enzymes CBP and p300. This work was supported by NIH grants AI118891, GM110174, CA196539 and AG031862 to B.A.G.; GM101664 to T.G.K.; K22ES26235, R21HD087866, R03CA211820 and a Pennsylvania Department of Health CURE grant to N.W.S.; R01 GM060293, R35 GM118090 and P01 AG031862 to R.M.; the NIH training grant fellowship T32GM008275 to D.M.M., and the NIH grant GM110174-S1 to M.C.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85032281711&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-01384-9
DO - 10.1038/s41467-017-01384-9
M3 - Article
C2 - 29070843
AN - SCOPUS:85032281711
SN - 2041-1723
VL - 8
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 1141
ER -