JmjC domain

Tsukada Y, Fang J, Erdjument-Bromage H, Warren ME, Borchers CH, Tempst P, Zhang Y (2006) Histone demethylation by a family of JmjC domain-containing proteins. Nature 439 811-816 van Holde K, Yager T (2003) Models for chromatin remodeling a critical comparison. Biochem Cell Biol 81 169-172... 

A large number of histone lysine methylation sites have been characterized, showing that the trimethylated state is prevalent. Given that LSDl demethylates only mono- and dimethylated lysine substrates, it seemed likely that additional enzymes would catalyze such a reaction. Indeed, the recent discovery of proteins that harbor a JmjC domain and have demethylase activity revealed a novel family of enzymes that also contain other domains associated with chromatin remodeling. 

Figure 13.5 The human Jumonji C family. Phylogenetic tree of the human JmjC domain containing proteins modified from Cloos et al. [3]. The domain structures of the proteins are indicated. The clusters for which histone lysine demethylase activity have been published are shown in gray. See text for details and references, jumonji C domain (JmjC) Jumonji...

Tsukada, Y, Fang, J., Erdjument-Bromage, H., Warren, M.E., Borchers, C.H., Tempst, P. and Zhang, Y. (2006) Histone demefhylation by a family of JmjC domain-containing proteins. Nature, 439, 811-816. 

Pfau, R., Tzatsos, A., Kampranis, S.C., Serebrennikova, O.B., Bear, S.E. and Tsichlis, P.N. (2008) Members of a family of JmjC domain-containing oncoproteins immortalize embryonic fibroblasts via a JmjC domain-dependent process. 

It shares homology with the JmjC domains found in the histone lysine demethylases. JMJD6 can demethylate H3 R2 and H4 R3 in biochemical and cell-based assays (42). The recent data that are emerging place histone arginine methylation as a key player of cell growth and cell proliferation processes. 

Klose RJ, Kallin EM, Zhang Y. JmjC-domain-containing proteins and histone demethylation. Nat. Rev. Genet. 2006 7 715-727. Benevolenskaya EV. Histone H3K4 demethylases are essential in development and differentiation. Biochem. Cell Biol. 2007 85 435-443. 

Figure 12 (a) Lys/Arg N-methylation (b) mechanism of FAD-dependent LSDl-catalyzed Lys demethylation (c) mechanism of Fe-dependent JHDM (JmjC domain-containing histone demethylase)-catalyzed demethylation. 

Figure 5.13 Histone demethylases. Structures and mechanisms are illustrated for the two subclasses of histone lysine demethylases. (a) Views from an X-ray crystal structure of LSDl (PDB ID 2V1D) in complex with cofactor FAD and a peptide substrate analogue, where methionine replaces methylated lysine, and outline mechanism of the LSDl-catalysed demethylation reaction, (b) Views from an X-ray crystal structure of JMJD2A (PDB ID 20Q6) in complex with co-factor analogue N-oxa-lylglycine and histone substrate trimethylated at H3K9 (note that Ni(II) replaces Fe(II) for crystallography), and outline mechanism of JmjC-domain catalysed lysine demethylation. (c) Representative inhibitors of LSDl and JmjC-domain demethylases.

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