Intracellular Crotonyl-CoA Stimulates Transcription through p300-Catalyzed Histone Crotonylation

Benjamin R. Sabari, Zhanyun Tang, He Huang, Vladimir Yong-Gonzalez, Henrik Molina, Ha Eun Kong, Lunzhi Dai, Miho Shimada, Justin R. Cross, Yingming Zhao, Robert G. Roeder, C. David Allis

Research output: Contribution to journalArticle

171 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)203-215
Number of pages13
JournalMolecular cell
Volume58
Issue number2
DOIs
StatePublished - Apr 16 2015
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    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. (2015). Intracellular Crotonyl-CoA Stimulates Transcription through p300-Catalyzed Histone Crotonylation. Molecular cell, 58(2), 203-215. https://doi.org/10.1016/j.molcel.2015.02.029