Histone Lysine methyltransferases
Lysine methyltransferases are the most widely studied and classified writers. All of these enzymes contain the evolutionarily conserved catalytic SET [Su(var)3-9, Enhancer-of-zeste, Trithorax] domain. They catalyse the transfer of methyl groups from S-Adenosyl methionine (SAM) to e-amino group of target lysine residues by an SN-2 mechanism.
There are mainly 7 important families of methyltransferases known till date. These include EZ, SET1, SET2, SMYD, SUV39, SUV4-20, RIZ as main families and SET8/PR-SET7 and SET7/9 as other families. Each family has a characteristic domain associated with SET. It could be Pre-Set, Post-set, PHD, Tudor etc.
We found 30 unique SET domain containing proteins belonging to the above mentioned families and capable of histone methylation through literature. Histone marks created by these enzymes can either activate transcription (H3K4me) or repress transcription (H3K27me, H2K9me). Hence the activity of these enzymes together helps in creation of bivalent chromatin marks in order to keep genes in a poised state (activation/repression). They play important role in many cellular processes like DNA replication, cell cycle progression, cytokinesis, transcriptional regulation of Hox genes and tumour suppressor genes, DNA damage response, replication stress response, X chromosome inactivation, and energy homeostasis. Another significant contribution is the regulation of master regulators like p53 and components of NF-kB pathway. They are also involved in maintenance of chromatin structure by creating marks that recruit heterochromatin protein (HP1) in order to initiate the process of heterochromatinisation.
A large amount of literature supports the role of lysine methyltransferases in cancers. Either the expression of these proteins is altered or they undergo mutations. For example MLLs and NSDs have been heavily implicated in multiple cancers like breast, lung, colorectal, different types of blood and prostate cancers. These proteins are also involved in Sotos syndrome, Huntingtons disease, Wolf-Hirschhorn syndrome and Weaver syndrome.Cytogenetic map of Lysine methyltransferases coding genes