EZ: Enhancer of Zeste is a Polycomb Group protein essential for the establishment and maintenance of repression of homeotic and other genes. In the early embryo it is found in a complex that includes ESC and is recruited to Polycomb Response Elements. We show that this complex contains a methyltransferase activity that methylates lysine 9 and lysine 27 of histone H3, but the activity is lost when the E(Z) SET domain is mutated. The lysine 9 position is trimethylated and this mark is closely associated with Polycomb binding sites on polytene chromosomes but is also found in centric heterochromatin, chromosome 4, and telomeric sites. Histone H3 methylated in vitro by the E(Z)/ESC complex binds specifically to Polycomb protein. (1)

Reference
1. Czermin B., Melfi R., McCabe D., Seitz V., Imhof A., Pirrotta V.Drosophila enhancer of Zeste/ESC complexes have a histone H3 methyltransferase activity that marks chromosomal Polycomb sites. Cell.2002;111(2):185-196. PMID: 12408863.

    HMT_other: Human SET7/9 mono-methylates H3K4, whereas S. cerevisiae SET1 di- or tri-methylates the same residue. The strict lysine specificity of these enzymes is in distinct contrast to Drosophila ASH1 (a member of the SET1 family), mammalian G9a, human EZH1 and EZH2 and mouse NSD1, enzymes that can methylate two or more different lysine residues. In some cases, the functions of SET-domain enzymes are not confined to histone methylation. For instance, human SET7/9 has recently been reported to methylate Lys189 in the general transcription factor TAF10, resulting in an increased affinity for RNA polymerase II and transcriptional activation of certain TAF10-dependent genes. SET7/9 has also been reported to methylate p53, increasing the stability of this short lived tumor-suppressor protein. (1)

Reference
1. Dillon SC, Zhang X, Trievel RC, Cheng XD.The SET-domain protein superfamily: protein lysine methyltransferases.Genome Biol.2005;6:227. PMID: 16086857.

    PRMT: The post-translational methylation of arginyl residues is catalyzed by a family of enzymes called protein arginine methyltransferases (PRMTs). Nine human PRMT isoforms are capable of forming monomethylarginine (MMA), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) on targeted proteins. Type I PRMTs form MMA and ADMA, and represent the majority of identified PRMTs. Type III enzymes, such as PRMT7, only produce MMA. Like the type I and III enzymes, type II PRMTs catalyze monomethylation; however, a second round of turnover results in the biologically distinct SDMA. A fourth type, Type IV, which results in the monomethylation of the internal guanidino nitrogen, has also been identified in yeast, but no mammalian homologue has been identified. (1)

Reference
1. Morales Y, Cáceres T, May K, Hevel JM.Biochemistry and regulation of the protein arginine methyltransferases (PRMTs). Arch Biochem Biophys.2016;590;52-138 PMID: 26612103.

    RIZ: RIZ is an Rb-binding protein and also a co-activator of the oestrogen receptor. It contains an N-terminal SET domain and a C-terminal domain that allows RIZ proteins to dimerize. The RIZ SET domain has previously been referred to as a PR-domain. To date, none of the RIZ proteins has been shown to possess methyltransferase activity, probably because of inappropriate assay conditions. (1)

Reference
1. Schneider R, Bannister AJ, Kouzarides T.Unsafe SETs: histone lysine methyltransferases and cancer. Trends Biochem Sci.2002;27(8):396-402. PMID: 12151224.

    SET1: The SET1 gene in the budding yeast Saccharomyces cerevisiae was discovered by several laboratories as encoding the first known H3K4 methyltransferase, a catalytic function performed through its conserved SET domain. Yeast Set1, like its orthologs in higher eukaryotes (SET1A/B in humans), is recruited to chromatin by the serine 5-phosphorylated C-terminal domain of RNA polymerase II (pol II). This interaction with the initiating form of pol II results in the occupancy of Set1 near the 5’-end of active genes, which correlates closely with the peak of H3K4me3. (1)

    In metazoans, SET1A/B proteins seem to function analogously to yeast Set1 in performing the majority of transcription-coupled H3K4 methylation found at active genes, presumably through co-transcriptional recruitment. Unlike their yeast counterpart, human SET1A/B proteins are also recruited to chromatin via an interaction with non-methylated CpG island sequences, mediated by the SET1A/B-associated protein CFP1.

Reference
1. Ernst P, Vakoc CR.WRAD: enabler of the SET1-family of H3K4 methyltransferases. Brief Funct Genomics.2012;11(3):217-226. PMID: 22652693.

    SET2: The founding member of this subfamily is the domain from the Saccharomyces cerevisiae SET2 protein (ySET2). This protein has intrinsic histone methyltransferase activity specific for H3 K36. Members of the mammalian nuclear receptor-binding SET-domain-containing (NSD) family contain a SET domain that is highly related to that of ySET2, leading to the suggestion that NSD proteins might be involved in chromatin regulation. However, NSD proteins have yet to be shown to possess methyltransferase activity, probably because of inappropriate assay conditions and/or addition of the incorrect substrate. In any case, based on the presence of a SET domain that is highly homologous to ySET2, we suggest that these proteins will eventually be shown to possess methyltransferase activity. (1)

Reference
1. Schneider R, Bannister AJ, Kouzarides T.Unsafe SETs: histone lysine methyltransferases and cancer. Trends Biochem Sci.2002;27(8):396-402. PMID: 12151224.

    SUV39: The Su(var)3-9 gene was originally identified in a genetic screen as a suppressor of position effect variegation in Drosophila. This was the first hint that the Su(var)3-9 protein might be involved in regulating chromatin structure. In mice, there are two highly related homologues of the Drosophila Su(var)3-9, Suv39h1 and Suv39h2. Following the identification of Suv39h1 as a lysine methyltransferase capable of methylating Lys9 of histone H3 (H3K9), confirmation that this protein can modulate chromatin architecture came with the finding that it creates a specific binding site for the heterochromatin protein HP1. As Suv39h1 and HP1 interact, it is thought that Suv39h1 methylating H3 K9, and then HP1 binding to the methylated H3, forms a positive feedback loop allowing HP1 and H3 K9 methylation to spread along chromatin, generating repressive heterochromatin in the process. (1)

Reference
1. Schneider R, Bannister AJ, Kouzarides T.Unsafe SETs: histone lysine methyltransferases and cancer. Trends Biochem Sci.2002;27(8):396-402. PMID: 12151224.

    SUV4-20: SUV4-20 subfamily methylates H4K20 in other species. Human, mouse, and Xenopus laevis have two SUV4-20 members, while in Drosophila and several other insects there is only one member. In silkworm, we identified only one SUV4-20 member like other insects. Phylogenetic analysis of SUV4-20 subfamily suggests that BmSuv4-20 clusters with Suv4-20 proteins of Drosophila, Anopheles gambiae, and other insects . Besides, SUV4-20 proteins of vertebrates cluster together. Among vertebrates, Suv4-20h2 (Suv4-20 homolog 2) of human and Rattus norvegicus are shorter than Suv4-20h1 (Suv4-20 homolog 1) and cluster together. BmSuv4-20 has the same domain structure as SUV4-20 proteins of other species that there is only one domain the SET located on the N-terminal of them20. (1)

Reference
1. Zhao H, Zheng C, Cui H.Identification and Analysis of the SET-Domain Family in Silkworm, Bombyx mori. Biomed Res Int.2015;2015:161287. PMID: 26558257.

    nonSET: Dot1/KMT4 histone lysine methyltransferases do not contain a SET domain and methylate Lys-79 within the core domain of histone H3. In addition, Dot1/KMT4 methyltransferases only methylate nucleosomal substrates, not free histones. Structures of Dot1/KMT4 methyltransferases with AdoMet or AdoHcy bound reveal an extended AdoMet conformation that is in stark contrast to the folded U-shaped conformation found in SET domain methyltransferases. Sequence analysis suggests that Dot1/KMT4 methyltransferases possess AdoMet binding motifs similar to histone arginine methyltransferase family. (1)

Reference
1. Smith BC, Denu JM.Chemical mechanisms of histone lysine and arginine modifications. Biochimica Et Biophysica Acta (BBA) - Gene Regulatory Mechanisms.2009;1789:45-57. PMID: 18603028.