SET domain lysine methyltransferase

Histone methylation participates in the regulation of gene expression patterns. Unlike histone acetylation, histone methylation does not alter the charge of the amino acid and hence the histone tail. There are changes in the basicity and the hydrophobicity which are relatively small when viewed at the scale of the histone but still influence the affinity of the histone tails to certain proteins, for example transcription factors, which in turn result in certain signaling events. The histone methyltransferases are usually subdivided into three classes SET domain lysine methyltransfeases, nonSET domain lysine methyltransferases and arginine methyltransferases (PRMTs). All of them utilize S-adenosylmethionine (SAM) as cosubstrate for the methylation reaction... 

Like the SET domain containing methyltransferases, PRMTs require AdoMet as a cofactor and methyl group donor. The PRMTs identified so far exist as members of multisubunit complexes, the formation of which is critical for in vivo methyltransferase activity (Teyssier et al., 2002). Many of the arginine methyltransferases also form homo-dimers or homooligomers, a step that is required for their catalytic activity (Weiss et al., 2000). This need to oligomerize has not been demonstrated for any known lysine methyltransferases. 

Yeates TO (2002) Structures of set domain proteins protein lysine methyltransferases make their mark. Cell 111 5-7... 

There is a school of thought, which believes that HMTases are tumor suppressors especially the lysine methyltransferases because of the loss of SET domain proteins in tumor conditions, exceptions do exist like Ezh2. The well-known example of the above is RIZl, which interacts with Rb protein (again the same tumor suppressor). RIZ-1 is in chromosome lp36 region, which is commonly deleted, in more than a dozen different types of human cancers. Riz-1 expression is commonly silenced in many tumors including breast cancer, liver cancer, colon cancer, neuroblastoma, melanoma, lung cancer and osteosarcoma (Kim et al, 2003). 

Histone lysine (K) methyltransferase (HKMTs) may lead to mono, di- and trimethy-lation of the E-amino group and the extent of modification at a specific site controls the recruitment of the effector proteins. Two unequally populated folds are presently known the SET domain-containing family and the Dotl family (for a recent review, see Ref. [70])... 

Qian, C. and Zhou, M.M. (2006) SET domain protein lysine methyltransferases Structure, specificity and catalysis. Cellular and Molecular Life Sciences, 63 (23), 2755-2763. 

Tachibana M, Sugimoto K, Fukushima T et al (2001) Set domain-containing protein, G9a, is a novel lysine-preferring mammalian histone methyltransferase with hyperactivity and specific selectivity to lysines 9 and 27 of histone H3. J Biol Chem 276 25309-25317... 

A SET Domain Containing Lysine-Specific Histone Methyltransferases. 207... 

Methylation of histone lysine residues is catalysed by site- and methylation-state specific i.e. tri-/di-/monomethylation states) histone methyltransferases (EC number 2.1.1.43, Table 5.4). With the exception of DOTIL, which methylates H3K79, all identified KMTs catalyse methylation using a SET domain (SET is an abbreviation for Su(var)3-9, Enhancer of zeste and Trithorax and refers to the Drosophila protein suppressor of variegation where this domain was first identified). ... 

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