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
Synonyms
SETD3, SETD7, WHSC1L1, Core MLL complex methylate lysine-5 of histone H3
ReviewStatus
5/5
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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
12670868 Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1

Laherty, CD, Myers, MP, Eisenman, RN, Herr, W, Wysocka, J

Genes Dev. 2003
17707229 Activator-mediated recruitment of the MLL2 methyltransferase complex to the beta-globin locus

Aebersold, R, Demers, C, Dilworth, FJ, Morle, F, Lai, P, Ranish, JA, Groudine, M, Juban, G, Chaturvedi, CP, Brand, M

Mol. Cell 2007
12540855 Structure and catalytic mechanism of the human histone methyltransferase SET7/9

Kelly, G, Walker, PA, Vasisht, N, Gamblin, SJ, Wilson, JR, Taylor, IA, Xiao, B, Jing, C, Howell, S, Blackburn, GM

Nature 2003
17500065 PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 methyltransferase complex

Ge, K, Guo, H, Hong, S, Hong, T, Yu, H, Copeland, TD, Kim, D, Dressler, GR, Guszczynski, T, Cho, YW, Kalkum, M

J. Biol. Chem. 2007
16682010 Characterization of a novel WHSC1-associated SET domain protein with H3K4 and H3K27 methyltransferase activity

Kee, HJ, Kim, SK, Kim, SM, Choe, NW, Kook, H, Kim, YS, Eom, GH, Kook, H, Kim, JY, Seo, SB

Biochem. Biophys. Res. Commun. 2006
12453418 MLL targets SET domain methyltransferase activity to Hox gene promoters

Hess, JL, Gibbs, D, Brock, HW, Briggs, SD, Martin, ME, Milne, TA, Allis, CD

Mol. Cell 2002
21832073 Histone methyltransferase SETD3 regulates muscle differentiation

Kee, HJ, Choe, N, Kim, DW, Kim, JY, Kook, H, Son, HJ, Seo, SB, Kim, KB, Park, HJ, Kim, JR, Eom, GH, Choi, SY, Kim, JH

J. Biol. Chem. 2011
17021013 Coactivator as a target gene specificity determinant for histone H3 lysine 4 methyltransferases

Roeder, RG, Lee, DK, Lee, B, Lee, J, Kwak, E, Lee, JW, Lee, SK, Dou, Y, Kong, YY, Lee, S

Proc. Natl. Acad. Sci. U.S.A. 2006
Participants
Participates
Catalyst Activity

histone H3 methyltransferase activity of SETD3, SETD7, WHSC1L1, Core MLL complex [nucleoplasm]

Orthologous Events
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