Histone-lysine N-methyltransferase SETD7

Definition:

Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Has also methyltransferase activity toward non-histone proteins such as CGAS, p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation. Monomethylates 'Lys-491' of CGAS, promoting interaction between SGF29 and CGAS (By similarity).

References:

[1]. Jing Huang, et al. Repression of p53 activity by Smyd2-mediated methylation. Nature. 2006 Nov 30;444(7119):629-32. [Content Brief]

[2]. Sergei Chuikov, et al. Regulation of p53 activity through lysine methylation. Nature. 2004 Nov 18;432(7015):353-60. [Content Brief]

[3]. Yanxuan Xiao, et al. RIOX1-demethylated cGAS regulates ionizing radiation-elicited DNA repair. Bone Res. 2022 Feb 24;10(1):19. [Content Brief]

[4]. Bing Xiao, et al. Structure and catalytic mechanism of the human histone methyltransferase SET7/9. Nature. 2003 Feb 6;421(6923):652-6. [Content Brief]

[5]. Antigone Kouskouti, et al. Gene-specific modulation of TAF10 function by SET9-mediated methylation. Mol Cell. 2004 Apr 23;14(2):175-82. [Content Brief]

[6]. Jean-François Couture, et al. Structural basis for the methylation site specificity of SET7/9. Nat Struct Mol Biol. 2006 Feb;13(2):140-6. [Content Brief]

[7]. Joost H A Martens, et al. Cascade of distinct histone modifications during collagenase gene activation. Mol Cell Biol. 2003 Mar;23(5):1808-16. [Content Brief]

[8]. H Wang, et al. Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase. Mol Cell. 2001 Dec;8(6):1207-17. [Content Brief]

[9]. Joshua Francis, et al. Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription. J Biol Chem. 2005 Oct 28;280(43):36244-53. [Content Brief]

[10]. Kenichi Nishioka, et al. Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation. Genes Dev. 2002 Feb 15;16(4):479-89. [Content Brief]

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