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

ABSTRACT:

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.cerevisiae strain which requires Jhd2 demethylase activity to efficiently grow in the presence of rapamycin. In order to validate the system we screened a library of 45 structurally different compounds designed as competitive inhibitors of α -ketoglutarate (α-KG) cof

SUBMITTER: Mannironi C 

PROVIDER: S-EPMC3906020 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature