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  • A selective inhibitor and probe of the cellular functions of Jumonji C domain-containing histone demethylases.

A selective inhibitor and probe of the cellular functions of Jumonji C domain-containing histone demethylases.

Journal of the American Chemical Society (2011-05-19)
Xuelai Luo, Yongxiang Liu, Stefan Kubicek, Johanna Myllyharju, Anthony Tumber, Stanley Ng, Ka Hing Che, Jessica Podoll, Tom D Heightman, Udo Oppermann, Stuart L Schreiber, Xiang Wang
PMID21585201
ABSTRACT

Histone methylations are important chromatin marks that regulate gene expression, genomic stability, DNA repair, and genomic imprinting. Histone demethylases are the most recent family of histone-modifying enzymes discovered. Here, we report the characterization of a small-molecule inhibitor of Jumonji C domain-containing histone demethylases. The inhibitor derives from a structure-based design and preferentially inhibits the subfamily of trimethyl lysine demethylases. Its methyl ester prodrug, methylstat, selectively inhibits Jumonji C domain-containing his-tone demethylases in cells and may be a useful small-molecule probe of chromatin and its role in epigenetics.