Reaction: 3 S-adenosyl-L-methionine + a [histone H3]-L-lysine79 = 3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine79 (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine79 = S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine79
(1b) S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine79 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine79
(1c) S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine79 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine-79
Other name(s): DOT1L (gene name); KMT4 (gene name)
Systematic name: S-adenosyl-L-methionine:[histone H3]-L-lysine79 N6-trimethyltransferase
Comments: The enzyme successively methylates the L-lysine79 residue of histone H3 (H3K79), ultimately generating a trimethylated form. These modifications influence the binding of chromatin-associated proteins. This is the only known methylation event of a lysine residue within the core region of a histone, as all other such modifications occur at the tail.
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Feng, Q., Wang, H., Ng, H.H., Erdjument-Bromage, H., Tempst, P., Struhl, K. and Zhang, Y. Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. Curr. Biol. 12 (2002) 1052-1058. [PMID: 12123582]
2. Ng, H.H., Feng, Q., Wang, H., Erdjument-Bromage, H., Tempst, P., Zhang, Y. and Struhl, K. Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. Genes Dev. 16 (2002) 1518-1527. [PMID: 12080090]
3. Min, J., Feng, Q., Li, Z., Zhang, Y. and Xu, R.M. Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. Cell 112 (2003) 711-723. [PMID: 12628190]
4. Steger, D.J., Lefterova, M.I., Ying, L., Stonestrom, A.J., Schupp, M., Zhuo, D., Vakoc, A.L., Kim, J.E., Chen, J., Lazar, M.A., Blobel, G.A. and Vakoc, C.R. DOT1L/KMT4 recruitment and H3K79 methylation are ubiquitously coupled with gene transcription in mammalian cells. Mol. Cell Biol. 28 (2008) 2825-2839. [PMID: 18285465]