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.

We show that in 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 and , which regulate the nuclear availability of α-ketoglutarate, which, as a cofactor for Jhd2 demethylase, regulates H3K4 tri-methylation.

An high-throughput in vivo screening system to select H3K4-specific histone demethylase inhibitors.

Background: Histone demethylases (HDMs) have a prominent role in epigenetic regulation and are emerging as potential therapeutic cancer targets. The search for small molecules able to inhibit HDMs in vivo is very active but at the present few compounds were found to be specific for defined classes of these enzymes.

Methodology/principal Findings: In order to discover inhibitors specific for H3K4 histone demethylation we set up a screening system which tests the effects of candidate small molecule inhibitors on a S.