Human KIAA1718 for use in assays to identify drugs that modulate activity of the enzyme or to engineer recombinant protein for use in such assays.
- Allows for the function of individual methyl marks to be identified.
- Applications towards mental retardation, cleft lip or palate, and other congenital abnormalities.
Jumonji-C (JmjC) domain-containing proteins catalyze histone demethylation via an oxidative pathway that requires the presence of Fe(II) and α-ketoglutarate as cofactors. The active removal of methyl groups from histones plays an essential role in epigenetic regulation. These enzymes are involved in a range of cellular processes including DNA replication and repair as well as transcriptional activation and repression.
Emory researchers have isolated the N-terminal domain, including the plant homeodomain (PHD) and the catalytic domain, of KIAA1718, a histone demethylase found in mice and humans that is selective for mono- and di-methylated lysine residues. The protein contains different segments for both recognizing and removing opposing methyl groups. While the PHD binds Lys4-trimethylated histone 3 (H3K4me3), an alteration associated with transcriptional activation, the jumonji (catalytic) domain demethylates H3K27me2, a mechanism associated with transcriptional repression. The enzymes’ catalytic activity and substrate specificity is thereby enhanced through the simultaneous binding of multiple domains. The ability to apprehend the function of individual methyl marks could lead to a marked understanding of the language of the histone code.
Publication: Horton J, et al. Nature. 17:38-43. (2010).