Human UTY(KDM6C) Is a Male-specific N(ϵ)-Methyl Lysyl Demethylase

The Jumonji C lysine demethylases (KDMs) are 2-oxoglutarate- and Fe(II)-dependent oxygenases. KDM6A (UTX) and KDM6B (JMJD3) are KDM6 subfamily members that catalyze demethylation of N(ϵ)-methylated histone 3 lysine 27 (H3K27), a mark important for transcriptional repression. Despite reports stating...

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Detalles Bibliográficos
Autores principales: Walport, Louise J., Hopkinson, Richard J., Vollmar, Melanie, Madden, Sarah K., Gileadi, Carina, Oppermann, Udo, Schofield, Christopher J., Johansson, Catrine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2014
Materias:
Enzymology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4140284/
https://www.ncbi.nlm.nih.gov/pubmed/24798337
http://dx.doi.org/10.1074/jbc.M114.555052
Descripción
Sumario:The Jumonji C lysine demethylases (KDMs) are 2-oxoglutarate- and Fe(II)-dependent oxygenases. KDM6A (UTX) and KDM6B (JMJD3) are KDM6 subfamily members that catalyze demethylation of N(ϵ)-methylated histone 3 lysine 27 (H3K27), a mark important for transcriptional repression. Despite reports stating that UTY(KDM6C) is inactive as a KDM, we demonstrate by biochemical studies, employing MS and NMR, that UTY(KDM6C) is an active KDM. Crystallographic analyses reveal that the UTY(KDM6C) active site is highly conserved with those of KDM6B and KDM6A. UTY(KDM6C) catalyzes demethylation of H3K27 peptides in vitro, analogously to KDM6B and KDM6A, but with reduced activity, due to point substitutions involved in substrate binding. The results expand the set of human KDMs and will be of use in developing selective KDM inhibitors.

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