Title: Recognition of Histone Crotonylation by Taf14 Links Metabolic State to Gene Expression.
Authors: Gowans, Graeme J; Bridgers, Joseph B; Zhang, Jibo; Dronamraju, Raghuvar; Burnetti, Anthony; King, Devin A; Thiengmany, Aline V; Shinsky, Stephen A; Bhanu, Natarajan V; Garcia, Benjamin A; Buchler, Nicolas E; Strahl, Brian D; Morrison, Ashby J
Published In Mol Cell, (2019 12 19)
Abstract: Metabolic signaling to chromatin often underlies how adaptive transcriptional responses are controlled. While intermediary metabolites serve as co-factors for histone-modifying enzymes during metabolic flux, how these modifications contribute to transcriptional responses is poorly understood. Here, we utilize the highly synchronized yeast metabolic cycle (YMC) and find that fatty acid β-oxidation genes are periodically expressed coincident with the β-oxidation byproduct histone crotonylation. Specifically, we found that H3K9 crotonylation peaks when H3K9 acetylation declines and energy resources become limited. During this metabolic state, pro-growth gene expression is dampened; however, mutation of the Taf14 YEATS domain, a H3K9 crotonylation reader, results in de-repression of these genes. Conversely, exogenous addition of crotonic acid results in increased histone crotonylation, constitutive repression of pro-growth genes, and disrupted YMC oscillations. Together, our findings expose an unexpected link between metabolic flux and transcription and demonstrate that histone crotonylation and Taf14 participate in the repression of energy-demanding gene expression.
PubMed ID: 31676231
MeSH Terms: Acyl Coenzyme A/metabolism*; Energy Metabolism*/genetics; Fatty Acids/metabolism; Gene Expression Regulation, Fungal*; Histones/genetics; Histones/metabolism*; Homeostasis; Lysine; Oxidation-Reduction; Protein Processing, Post-Translational*; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism*; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism*; Signal Transduction; Transcription Factor TFIID/genetics; Transcription Factor TFIID/metabolism*; Transcription, Genetic