Reaction: 2 S-adenosyl-L-methionine + a [histone H3]-L-lysine36 = 2 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine36 (overall reaction)
(1a) S-adenosyl-L-methionine + a [histone H3]-L-lysine36 = S-adenosyl-L-homocysteine + a [histone H3]-N6-methyl-L-lysine36
(1b) S-adenosyl-L-methionine + a [histone H3]-N6-methyl-L-lysine36 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6-dimethyl-L-lysine36
Other name(s): KMT3B (gene name); KMT3C (gene name); NSD2 (gene name); NSD3 (gene name); SETMAR (gene name); WHSC1 (gene name)
Systematic name: S-adenosyl-L-methionine:[histone H3]-L-lysine36 N6-dimethyltransferase
Comments: This entry describes a group of metazoan enzymes that catalyse two successive methylations of lysine 36 of histone H3 (H3K36), forming mono- and dimethylated forms. These modifications influence the binding of chromatin-associated proteins. The product can be further methylated to the trimethyl form by EC 2.1.1.358, histone H3 dimethyl-L-lysine36 N-methyltransferase. The yeast SET2 enzyme can catalyse all three methylations (see EC 2.1.1.359, histone H3 lysine36 N-trimethyltransferase).
Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:
References:
1. Fnu, S., Williamson, E.A., De Haro, L.P., Brenneman, M., Wray, J., Shaheen, M., Radhakrishnan, K., Lee, S.H., Nickoloff, J.A. and Hromas, R. Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous end-joining. Proc. Natl Acad. Sci. USA 108 (2011) 540-545. [PMID: 21187428]
2. Kuo, A.J., Cheung, P., Chen, K., Zee, B.M., Kioi, M., Lauring, J., Xi, Y., Park, B.H., Shi, X., Garcia, B.A., Li, W. and Gozani, O. NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming. Mol. Cell 44 (2011) 609-620. [PMID: 22099308]
3. Qiao, Q., Li, Y., Chen, Z., Wang, M., Reinberg, D. and Xu, R.M. The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation. J. Biol. Chem 286 (2011) 8361-8368. [PMID: 21196496]
4. Wagner, E.J. and Carpenter, P.B. Understanding the language of Lys36 methylation at histone H3. Nat. Rev. Mol. Cell. Biol. 13 (2012) 115-126. [PMID: 22266761]