IUBMB Enzyme Nomenclature


Accepted name: histone H3 lysine36 N-trimethyltransferase

Reaction: 3 S-adenosyl-L-methionine + a [histone H3]-L-lysine36 = 3 S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-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
(1c) S-adenosyl-L-methionine + a [histone H3]-N6,N6-dimethyl-L-lysine36 = S-adenosyl-L-homocysteine + a [histone H3]-N6,N6,N6-trimethyl-L-lysine36

Other name(s): SET2 (gene name)

Systematic name: S-adenosyl-L-methionine:[histone H3]-L-lysine36 N6-trimethyltransferase

Comments: The enzyme, characterized from yeast, catalyses the successive methylation of lysine36 of histone H3 (H3K36), forming the trimethylated form. These modifications influence the binding of chromatin-associated proteins. The enzyme couples the methylation reactions with transcriptional elongation through an interaction with the large subunit of RNA polymerase II. In mammals this activity is catalysed by two different enzymes, EC, histone H3 lysine36 N-dimethyltransferase and EC, histone H3 dimethyl-L-lysine36 N-methyltransferase.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, PDB, CAS registry number:


1. Strahl, B.D., Grant, P.A., Briggs, S.D., Sun, Z.W., Bone, J.R., Caldwell, J.A., Mollah, S., Cook, R.G., Shabanowitz, J., Hunt, D.F. and Allis, C.D. Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression. Mol. Cell Biol. 22 (2002) 1298-1306. [PMID: 11839797]

2. Landry, J., Sutton, A., Hesman, T., Min, J., Xu, R.M., Johnston, M. and Sternglanz, R. Set2-catalyzed methylation of histone H3 represses basal expression of GAL4 in Saccharomyces cerevisiae. Mol. Cell Biol. 23 (2003) 5972-5978. [PMID: 12917322]

3. Morris, S.A., Shibata, Y., Noma, K., Tsukamoto, Y., Warren, E., Temple, B., Grewal, S.I. and Strahl, B.D. Histone H3 K36 methylation is associated with transcription elongation in Schizosaccharomyces pombe. Eukaryot Cell 4 (2005) 1446-1454. [PMID: 16087749]

4. Lin, L.J., Minard, L.V., Johnston, G.C., Singer, R.A. and Schultz, M.C. Asf1 can promote trimethylation of H3 K36 by Set2. Mol. Cell Biol. 30 (2010) 1116-1129. [PMID: 20048053]

[EC created 2019]

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