The nucleosome, made up of four core histone proteins (H2A, H2B, H3 and H4), is the primary building block of chromatin. Histones have been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation and ubiquitination. Histone methylation is a major determinant for the formation of active and inactive regions of the genome and is crucial for the proper programming of the genome during development. A diverse set of histone lysine methyltransferases has been identified, all but one of which contain a SET domain originally identified in the Drosophila, Enhancer of zeste and Trithorax proteins. Lysine methylation occurs primarily on histones H3 (Lys4, 9, 27, 36, 79) and H4 (Lys20) and has been implicated in both transcriptional activation and silencing. Methylation of these lysine residues induces the recruitment of chromatin modifying enzymes containing methyl-lysine binding modules. The discovery in 2004 of the histone demethylase LSD1, followed by the Jumonji demethylases JMJD1, JMJD2 and JHDM1 has shown that methylation is a reversible epigenetic process controlling cellular events.