Histone demethylase KDM5A removes methyl marks from lysine 4 of histone H3 and is often overexpressed in cancer.
However, recent studies show that the histone lysine methylation is not irreversible and histone lysine demethylases (HDMs) are employed for the removal of the methyl marks from the lysine residues of the histones [11], [12].
Acetylation marks are removed by histone deacetylases (HDACs), whereas histone demethylases are responsible for removing methyl marks from histones.
Demethylases containing the JmjC domain can catalyze the removal of all methylation marks (Huang et al., 2006; Tsukada et al., 2006), but different classes of JmjC proteins are only capable of removing a subset of methyl marks from specific lysine residues in vivo (Allis et al., 2007).
The discovery in mammals of two classes of enzyme that are able to demethylate histones lysine-specific demethistones lysine-specificl, 2004) andemethylase (JmjC) domain-containing proteins (Klose et al, 2006)—revealed that active removal of methyl marks from histones is necessary for proper epigenetic regulation.
The resulting shift from a silent methyl mark to that of acetylation is accompanied by a general upregulation of bivalent genes in the absence of PRC2.
In addition to normal DNA methylation, variations and derivatives of the methyl mark on CpG dinucleotides have also been reported, including hydroxymethyl, formyl, and carboxyl groups, as well as methyl marks that occur at non‐CpG sites.
The chromodomain protein Chd1 recognizes the lysine methyl mark and has been shown to promote transcriptional elongation [41], [42].
These results suggest that the H3 K36 methyl mark is required for nucleosomal retention during transcription elongation.
This methyl mark appears to serve as a basic recruitment signal for several factors.
