H3 lysine 4 methylation is required for full activation of genes involved in α-ketoglutarate availability in the nucleus of yeast cells after diauxic shift

Di Nisio, Elena; Danovska, Svetlana; Condemi, Livia; Cirigliano, Angela; Rinaldi, Teresa; Licursi, Valerio; Negri, Rodolfo

doi:http://dx.doi.org/10.3390/metabo13040507

H3 lysine 4 methylation is required for full activation of genes involved in α-ketoglutarate availability in the nucleus of yeast cells after diauxic shift

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Citation

Di Nisio E, Danovska S, Condemi L, Cirigliano A, Rinaldi T, Licursi V, Negri R. H3 lysine 4 methylation is required for full activation of genes involved in α-ketoglutarate availability in the nucleus of yeast cells after diauxic shift. Metabolites. 2023 Mar 31;13(4):507. DOI: 10.3390/metabo13040507

Abstract

We show that in S. cerevisiae the metabolic diauxic shift is associated with a H3 lysine 4 tri-methylation (H3K4me3) increase which involves a significant fraction of transcriptionally induced genes which are required for the metabolic changes, suggesting a role for histone methylation in their transcriptional regulation. We show that histone H3K4me3 around the start site correlates with transcriptional induction in some of these genes. Among the methylation-induced genes are IDP2 and ODC1, which regulate the nuclear availability of α-ketoglutarate, which, as a cofactor for Jhd2 demethylase, regulates H3K4 tri-methylation. We propose that this feedback circuit could be used to regulate the nuclear α-ketoglutarate pool concentration. We also show that yeast cells adapt to the absence of Jhd2 by decreasing Set1 methylation activity.