Metabolites (Mar 2023)

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

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

DOI
https://doi.org/10.3390/metabo13040507
Journal volume & issue
Vol. 13, no. 4
p. 507

Abstract

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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.

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