TY - JOUR
T1 - Recognition of Histone Crotonylation by Taf14 Links Metabolic State to Gene Expression
AU - Gowans, Graeme J.
AU - Bridgers, Joseph B.
AU - Zhang, Jibo
AU - Dronamraju, Raghuvar
AU - Burnetti, Anthony
AU - King, Devin A.
AU - Thiengmany, Aline V.
AU - Shinsky, Stephen A.
AU - Bhanu, Natarajan V.
AU - Garcia, Benjamin A.
AU - Buchler, Nicolas E.
AU - Strahl, Brian D.
AU - Morrison, Ashby J.
N1 - Funding Information:
We thank members of the Morrison and Strahl labs for suggestions and helpful discussions. We also thank Joseph Reese for the Taf14 antibody, Jerome Govin for the Bdf1/2 antibody, and Steve Hahn for various Taf antibodies. This work was supported by NIH grant GM126900 to B.D.S. and grant GM119580 to A.J.M. S.A.S. was supported by a UNC Lineberger Comprehensive Cancer Center postdoctoral fellowship and NIH grant F32GM125141 . D.A.K. was supported by a NSF pre-doctoral fellowship ( DGE 1656518 ).
Funding Information:
We thank members of the Morrison and Strahl labs for suggestions and helpful discussions. We also thank Joseph Reese for the Taf14 antibody, Jerome Govin for the Bdf1/2 antibody, and Steve Hahn for various Taf antibodies. This work was supported by NIH grant GM126900 to B.D.S. and grant GM119580 to A.J.M. S.A.S. was supported by a UNC Lineberger Comprehensive Cancer Center postdoctoral fellowship and NIH grant F32GM125141. D.A.K. was supported by a NSF pre-doctoral fellowship (DGE 1656518). J.B.B. B.D.S. A.J.M. and G.J.G. conceived the YMC project with inputs from A.B. R.D. and N.E.B. J.B.B. R.D. and A.B. collected YMC time points, and J.B.B. performed westerns and the ChIP experiments for sequencing. G.J.G. generated the ChIP-seq and RNA-seq libraries with assistance from D.A.K. and analyzed the data with assistance from A.J.M. G.J.G. and J.Z. also performed western blots and the crotonic acid addition experiments with assistance from A.V.T. J.Z. performed qRT-PCR experiments, and S.A.S. performed the ITC studies. N.V.B. and B.A.G. performed mass spectrometric experiments. A.J.M. B.D.S. and G.J.G. wrote the manuscript with input from all authors. The authors declare no competing interests.
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/12/19
Y1 - 2019/12/19
N2 - 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. Adaptive responses during environmental nutrient fluctuations are critical for survival. For example, during nutrient limitation, energy-demanding cell growth programs need to be tempered. Gowans et al. report that histone crotonylation, produced by fatty acid β-oxidation, is important for reduction of growth gene expression and promotion of metabolic homeostasis.
AB - 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. Adaptive responses during environmental nutrient fluctuations are critical for survival. For example, during nutrient limitation, energy-demanding cell growth programs need to be tempered. Gowans et al. report that histone crotonylation, produced by fatty acid β-oxidation, is important for reduction of growth gene expression and promotion of metabolic homeostasis.
UR - http://www.scopus.com/inward/record.url?scp=85076484415&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2019.09.029
DO - 10.1016/j.molcel.2019.09.029
M3 - Article
C2 - 31676231
AN - SCOPUS:85076484415
SN - 1097-2765
VL - 76
SP - 909-921.e3
JO - Molecular cell
JF - Molecular cell
IS - 6
ER -