|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Luo, X, Liu, Y, Kubicek, S, Myllyharju, J, Tumber, A, Ng, S, Che, KH, Podoll, J, Heightman, TD, Oppermann, U, Schreiber, SL, Wang, X|
|Journal||Journal of the American Chemical Society|
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.