Core MLL complex, SMYD3, PRDM9 methylate dimethyl-lysine-5 of histone H3 (H3K4)

Stable Identifier
Reaction [transition]
Homo sapiens
Core MLL complex, SMYD3, PRDM9 methylate Me2K5-histone H3
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Trimethylation 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 the 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).

SMYD3 (KMT3E) and PRDM9 (KMT8B) are able to tri-methylate H3K4 (Hamamoto et al. 2004, Hayashi et al. 2005, Koh-Stenta et al. 2014).

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
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
14992727 Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus

Hess, JL, Levine, SS, Meyerson, M, Hughes, CM, Bhattacharjee, A, Copeland, TD, Milne, TA, Shanmugam, KS, Kay, GF, Hayes, DN, Rozenblatt-Rosen, O, Biondi, CA, Lee, JC, Hayward, NK

Mol. Cell 2004
15235609 SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells

Hamamoto, R, Nakamura, Y, Morita, M, Li, M, Silva, FP, Iimura, Y, Yagyu, R, Furukawa, Y

Nat. Cell Biol. 2004
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
16292313 A histone H3 methyltransferase controls epigenetic events required for meiotic prophase

Matsui, Y, Yoshida, K, Hayashi, K

Nature 2005
16199523 MLL associates specifically with a subset of transcriptionally active target genes

Hess, JL, Roeder, RG, Brock, HW, Martin, ME, Milne, TA, Dou, Y

Proc. Natl. Acad. Sci. U.S.A. 2005
Catalyst Activity

histone H3 methyltransferase activity of Core MLL complex, SMYD3, PRDM9 [nucleoplasm]

This event is regulated