Reactome | SETD3, SETD7 (KMT7), WHSC1L1 (KMT3F), Core MLL complex methylate lysine-5 of histone H3 (H3K4)

SETD3, SETD7 (KMT7), WHSC1L1 (KMT3F), Core MLL complex methylate lysine-5 of histone H3 (H3K4)

Stable Identifier

R-HSA-5159245

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

Synonyms

SETD3, SETD7, WHSC1L1, Core MLL complex methylate lysine-5 of histone H3

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SETD3, SETD7 (KMT7), WHSC1L1 (KMT3F), Core MLL complex methylate lysine-5 of histone H3 (H3K4)

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Tri-methylation of lysine-5 of histone H3 (H3K4) has been linked to transcriptional activation in a variety of eukaryotic species (Ruthenberg et al. 2007). Several H3K4 methyltransferases have been identified in mammals, predominantly members of the Mixed Lineage Leukemia (MLL) protein family. Five of these, KMT2A (MML1), KMT2D (MLL2), KMT2C (MLL3), KMT2B (MLL4) and SETD1A (KMT2F) have been shown to display H3K4 mono-, di- and tri-methyltransferase activity (Milne et al. 2002, Hughes et al. 2004, Cho et al. 2007, Wysocka et al. 2003). KMT2G (SETD1B) is believed to have similar activity on the basis of sequence homology (Ruthenberg et al. 2007). MLLs are a component of large multiprotein complexes that also include WDR5, RBBP5, ASH2 and DPY30, assembled to form the core MLL complex (Nakamura et al. 2002, Hughes et al. 2004, Dou et al. 2006, Tremblay et al. 2014). The WD40 domain of WDR5 recognizes and binds the histone H3 N-terminus, presenting the lysine-4 side chain for methylation by one of the catalytically active MLL family (Couture et al. 2006, Ruthenburg et al. 2006). Histone H3 recognition by WDR5 is regulated by the methylation state of adjacent arginine (H3R2) residue. H3R2 methylation abolishes WDR5 interaction with the H3 histone tail (Couture et al. 2006); H3K4 di-/trimethylation and H3R2 methylation have an inverse relationship (Guccione et al. 2006).

SETD7 (KMT7, SET9, SET7/9) is an H3K4 mono-methytransferase (Wang et al. 2001, Xiao et al. 2003, Hu & Zhang 2006) that can also methylate a wide range of non-histone proteins (Dhayalan et al. 2011). SETD3 can mono- and di-methylate H3K4 and H3K36 (Eom et al. 2011).

Literature References

PubMed ID	Title	Journal	Year
17707229	Activator-mediated recruitment of the MLL2 methyltransferase complex to the beta-globin locus Demers, C, Chaturvedi, CP, Ranish, JA, Juban, G, Lai, P, Morle, F, Aebersold, R, Dilworth, FJ, Groudine, M, Brand, M	Mol. Cell	2007
12670868	Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1 Wysocka, J, Myers, MP, Laherty, CD, Eisenman, RN, Herr, W	Genes Dev.	2003
12540855	Structure and catalytic mechanism of the human histone methyltransferase SET7/9 Xiao, B, Jing, C, Wilson, JR, Walker, PA, Vasisht, N, Kelly, G, Howell, S, Taylor, IA, Blackburn, GM, Gamblin, SJ	Nature	2003
17500065	PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex Cho, YW, Hong, T, Hong, S, Guo, H, Yu, H, Kim, D, Guszczynski, T, Dressler, GR, Copeland, TD, Kalkum, M, Ge, K	J. Biol. Chem.	2007
16682010	Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity Kim, SM, Kee, HJ, Eom, GH, Choe, NW, Kim, JY, Kim, YS, Kim, SK, Kook, H, Kook, H, Seo, SB	Biochem. Biophys. Res. Commun.	2006
12453418	MLL targets SET domain methyltransferase activity to Hox gene promoters Milne, TA, Briggs, SD, Brock, HW, Martin, ME, Gibbs, D, Allis, CD, Hess, JL	Mol. Cell	2002
21832073	Histone methyltransferase SETD3 regulates muscle differentiation Eom, GH, Kim, KB, Kim, JH, Kim, JY, Kim, JR, Kee, HJ, Kim, DW, Choe, N, Park, HJ, Son, HJ, Choi, SY, Kook, H, Seo, SB	J. Biol. Chem.	2011
17021013	Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferases Lee, S, Lee, DK, Dou, Y, Lee, J, Lee, B, Kwak, E, Kong, YY, Lee, SK, Roeder, RG, Lee, JW	Proc. Natl. Acad. Sci. U.S.A.	2006