Disease relevance of SETD7

• To delineate the underlying mechanism, we investigated the role of two H3K4 methyltransferases, Set1 and Set7/9, in the lytic infection of HSV-1 [1].

High impact information on SETD7

• Set9 methylates specifically lysine 4 (K4) of histone H3 (H3-K4) and potentiates transcription activation [2].
• Methylation of histone H3-K4 by Set9 precludes the association of NuRD with the H3 tail [2].
• We demonstrate that SET7/9 can transfer two but not three methyl groups to unmodified Lys4 of H3 without substrate dissociation [3].
• Here we report the structure of the SET7/9 protein in the absence and presence of its cofactor product, S-adenosyl-L-homocysteine (AdoHcy) [4].
• Genotyping of Weber Screening Set 9 (387 short tandem-repeat polymorphisms with average spacing approximately 9 cM [range 1-19 cM]) was performed by the Mammalian Genotyping Service of Marshfield Laboratory. Presented here are the results for the 366 autosomal markers [5].

Biological context of SETD7

• Structural basis for the methylation site specificity of SET7/9 [6].
• Set9 specifically methylates p53 at one residue within the carboxyl-terminus regulatory region [7].
• We find that Set9-mediated methylation of Lys 372 inhibits Smyd2-mediated methylation of Lys 370, providing regulatory cross-talk between post-translational modifications [8].
• Using small interference RNA, we found that the reduction of Set1, but not Set7/9, reduces the transcription and replication of HSV-1 and specifically decreases H3K4me3 on the virus genome [1].

Associations of SETD7 with chemical compounds

• Collectively, our data reveal that SET7/9 recognizes a conserved K/R-S/T/A motif preceding the lysine substrate and has a propensity to bind aspartates and asparagines on the C-terminal side of the lysine target [6].
• Chromatin immunoprecipitation revealed that SET7/9 small interfering RNA could reduce TNF-alpha-induced recruitment of NF-kappaB p65 to inflammatory gene promoters [9].

Regulatory relationships of SETD7

• Set9 regulates the expression of p53 target genes in a manner dependent on the p53-methylation site [7].

Other interactions of SETD7

• Human SET7/9 is a protein lysine methyltransferase (PKMT) that methylates histone H3, the tumor suppressor p53 and the TBP-associated factor TAF10 [6].
• Thus, translocations of the MLL gene, by itself coding for a histone H3K4 methyltransferase, are presumably not randomly chosen, rather functionally selected.Leukemia (2006) 20, 777-784. doi:10.1038/sj.leu.2404150; published online 2 March 2006 [10].

References