Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation Journal Article


Authors: Sabari, B. R.; Tang, Z.; Huang, H.; Yong-Gonzalez, V.; Molina, H.; Kong, H. E.; Dai, L.; Shimada, M.; Cross, J. R.; Zhao, Y.; Roeder, R. G.; Allis, C. D.
Article Title: Intracellular crotonyl-CoA stimulates transcription through p300-catalyzed histone crotonylation
Abstract: Acetylation of histones at DNA regulatory elements plays a critical role in transcriptional activation. Histones are also modified by other acyl moieties, including crotonyl, yet the mechanisms that govern acetylation versus crotonylation and the functional consequences of this "choice" remain unclear. We show that the coactivator p300 has both crotonyltransferase and acetyltransferase activities, and that p300-catalyzed histone crotonylation directly stimulates transcription to a greater degree than histone acetylation. Levels of histone crotonylation are regulated by the cellular concentration of crotonyl-CoA, which can be altered through genetic and environmental perturbations. In a cell-based model of transcriptional activation, increasing or decreasing the cellular concentration of crotonyl-CoA leads to enhanced or diminished gene expression, respectively, which correlates with the levels of histone crotonylation flanking the regulatory elements of activated genes. Our findings support a general principle wherein differential histone acylation (i.e., acetylation versus crotonylation) couples cellular metabolism to the regulation of gene expression. © 2015 Elsevier Inc.
Journal Title: Molecular Cell
Volume: 58
Issue: 2
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2015-04-16
Start Page: 203
End Page: 215
Language: English
DOI: 10.1016/j.molcel.2015.02.029
PROVIDER: scopus
PUBMED: 25818647
PMCID: PMC4501262
DOI/URL:
Notes: Export Date: 4 May 2015 -- Source: Scopus
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  1. Justin Robert Cross
    99 Cross