This work uncovers a novel and biologically significant mechanism that directly connects nutrient availability to histone modifications and gene transcription. We report that glycolysis promotes histone H3K4 trimethylation (H3K4me3) by activating Tpk2, a catalytic subunit of protein kinase A (PKA) via the Ras-cyclic AMP (cAMP) pathway. Glucose-activated PKA (Tpk2) inhibits Jhd2-catalyzed H3K4 demethylation by phosphorylating Jhd2 at serine 321 and serine 340. In addition, Tpk2- catalyzed Jhd2 phosphorylation promotes H3K14ac by preventing the binding of Rpd3 at chromatin.