JmjC Domain-Containing Demethylases

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...

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. 

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. 

---