Document Detail


Quantitative dynamics of the link between cellular metabolism and histone acetylation.
MedLine Citation:
PMID:  23482559     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acetylation on the tails of histones plays an important role in controlling transcription initiation. Although the steady-state abundances of histone acetyl groups have been reported, the rate at which histones are acetylated and deacetylated on a residue-specific basis has not been quantitatively established. We added [(13)C]glucose to human cells and monitored the dynamic incorporation of (13)C-labeled acetyl groups onto specific histone lysines with quantitative mass spectrometry. We determined the turnover of acetylation to be generally slower than phosphorylation, but fast relative to methylation, and that the rate varied depending on the histone, the residue modified, and also the neighboring modifications. Cells were also treated with a deacetylase inhibitor to determine the rate due to histone acetyltransferase activity alone and in the absence of deacetylase activity. Introduction of (13)C-labeled glucose also resulted in the incorporation of (13)C into alanine, which allowed us to partition histones into existing and newly synthesized protein categories. Newly synthesized histones were slower to accumulate histone modifications, especially modifications associated with silent chromatin. Finally, we applied our new approaches to find that quiescent fibroblasts exhibited lower levels of labeled acetyl accumulation compared with proliferating fibroblasts. This suggests that acetylation rates can be modulated in cells in different biological states and that these changes can be detected with the approach presented here. The methods we describe can be broadly applied to defining the turnover of histone acetylation in other cell states such as during cellular reprogramming and to quantify non-histone protein acetylation dynamics.
Authors:
Adam G Evertts; Barry M Zee; Peter A Dimaggio; Michelle Gonzales-Cope; Hilary A Coller; Benjamin A Garcia
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-03-12
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  288     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-29     Completed Date:  2013-06-24     Revised Date:  2014-05-07    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  12142-51     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Acetylation
Alanine / metabolism*
Glucose / metabolism*
HEK293 Cells
Histones / metabolism*
Humans
Protein Processing, Post-Translational / physiology*
Grant Support
ID/Acronym/Agency:
5T32CA009528/CA/NCI NIH HHS; 5T32HG003284/HG/NHGRI NIH HHS; DP2OD007447/OD/NIH HHS
Chemical
Reg. No./Substance:
0/Histones; IY9XDZ35W2/Glucose; OF5P57N2ZX/Alanine
Comments/Corrections

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