GSE175868
Genome-wide maps of chromatin modifiers and histone modification in saccharomyces cerevisiae
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 poorly understood. Here, we report that glycolysis promotes H3K4me3 by activating Tpk2, the catalytic subunit of protein kinase A (PKA) via the Ras-cyclic AMP (cAMP) pathway. Further study showed that Tpk2 antagonizes Jhd2-catalyzed H3K4 demethylation by phosphorylating Jhd2 at S321 and S340 in response to glucose availability.Mechanistically, Tpk2-catalyzed Jhd2 phosphorylation inhibits its overall binding to chromatin and promotes its polyubiquitination by the E3 ubiquitin ligase Not4 and degradation by the proteasome. In addition, Tpk2-catalyzed Jhd2 phosphorylation also maintains H3K14ac by preventing the binding of Rpd3 to chromatin. By inhibiting the activity of Jhd2 and Rpd3, Tpk2-catalyzed Jhd2 phosphorylation regulates gene expression and promotes autophagy. Thus, regulation of Jhd2 by the Ras-cAMP-PKA pathway shed lights on how cells rewire their biological responses to glucose availability. Overall design: ChIP-Seq examination of Histone H3 and H3K4me3 as well as Jhd2 and Rpd3 in WT, Jhd2 S2A mutant .