In eukaryotes, transcription is regulated in part by post-translational modifications of histone proteins within chromatin. These modifications are dynamically regulated by chromatin-modifying enzymes. The jumonji family of histone demethylases are Fe(II)- and alpha-ketoglutarate-dependent chromatin modifiers that antagonize lysine methylation. Despite their crucial roles in the regulation of transcription in physiology and disease, mechanisms by which demethylases are recruited to and regulated at their target loci are poorly understood. Herein, we will present our findings on the catalysis and regulation of jumonji histone demethylases on homogeneous, site-selectively modified nucleosome substrates. To gain insight into the regulation of demethylases by chromatin, we have developed a quantitative assay to assess the demethylation of nucleosomes (Shiau C, Trnka MJ, Bozicevic A, Ortiz Torres I, Al-Sady B, Burlingame AL, Narlikar GJ, Fujimori DG. Chem Biol. 20: 494-9, 2013), and have applied this method to several demethylases. Our results point to the critical role of chromatin in regulating catalysis by these enzymes.

Bioinorganic catalysis on chromatin: Exploring regulation of histone demethylases

248th National Meeting (2014)

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