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.

    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.