Shihao Zhang
Xuanyunjing Gong
Qi Yu
Yuan Zhang
Mingdan Luo
Xianhua Zhang
Jerry L. Workman
Xilan Yu
Shanshan Li
aState Key Laboratory of Biocatalysis and Enzyme Engineering, College of Life Sciences, Hubei University, Wuhan, Hubei, 430062, China
bStowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO, 64110, USA
More InformationCorresponding author: E-mail address: xhzhang0072@hubu.edu.cn (Xianhua Zhang);E-mail address: yuxilan@hubu.edu.cn (Xilan Yu);E-mail address: shl@hubu.edu.cn (Shanshan Li)
Received Date: 2019-08-17
Accepted Date:2019-11-25
Rev Recd Date:2019-11-18
Available Online: 2019-12-11 Publish Date:2019-12-20
Abstract
Abstract
Cells need to coordinate gene expression with their metabolic states to maintain cell homeostasis and growth. However, how cells transduce nutrient availability to appropriate gene expression response via histone modifications remains largely unknown. Here, we report that glucose specifically induces histone H3K4 trimethylation (H3K4me3), an evolutionarily conserved histone covalent modification associated with active gene transcription, and that glycolytic enzymes and metabolites are required for this induction. Although glycolysis supplies S-adenosylmethionine for histone methyltransferase Set1 to catalyze H3K4me3, glucose induces H3K4me3 primarily by inhibiting histone demethylase Jhd2-catalyzed H3K4 demethylation. Glycolysis provides acetyl-CoA to stimulate histone acetyltransferase Gcn5 to acetylate H3K14, which then inhibits the binding of Jhd2 to chromatin to increase H3K4me3. By repressing Jhd2-mediated H3K4 demethylation, glycolytic enzymes regulate gene expression and cell survival during chronological aging. Thus, our results elucidate how cells reprogram their gene expression programs in response to glucose availability via histone modifications.Keywords: Gene transcription,
Glycolysis,
Histone modifications,
Yeast,
H3K4me3,
H3K14ac
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