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

  • J Am Chem Soc. 2011 Jun 22;133(24):9451-6. doi: 10.1021/ja201597b.
Xuelai Luo  1 ,  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
Affiliations
  • 1. Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA.
PMID: 21585201 DOI: 10.1021/ja201597b
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.

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