KDM7A
Domain
The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 prevents its access to H3K9me2.
The linker region is a critical determinant of demethylase specificity. It prevents the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3, while it favors selectivity toward H3K27me2.
Function
Histone demethylase required for brain development. Specifically demethylates dimethylated 'Lys-9', 'Lys-27' and 'Lys-36' (H3K9me2, H3K27me2, H3K36me2, respectively) of histone H3 and monomethylated histone H4 'Lys-20' residue (H4K20Me1), thereby playing a central role in histone code (PubMed:20023638, PubMed:20622853). Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: in presence of H3K4me3, it has no demethylase activity toward H3K9me2, while it has high activity toward H3K27me2. Demethylates H3K9me2 in absence of H3K4me3 (PubMed:20023638). Has activity toward H4K20Me1 only when nucleosome is used as a substrate and when not histone octamer is used as substrate (PubMed:20622853).
Sequence Similarities
Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily.
Cellular localization
- Nucleus
Alternative names
JHDM1D, KDM7, KIAA1718, KDM7A, Lysine-specific demethylase 7A, JmjC domain-containing histone demethylation protein 1D, Lysine-specific demethylase 7, [histone H3]-dimethyl-L-lysine9 demethylase 7A