Structure and CTD binding of the Set2 SRI domainStructure and CTD binding of the Set2 SRI domain
Structural highlights
2c5z is a 1 chain structure with sequence from Saccharomyces cerevisiae. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
SET2_YEAST Histone methyltransferase that trimethylates histone H3 'Lys-36' forming H3K36me3. Involved in transcription elongation as well as in transcription repression. The methyltransferase activity requires the recruitment to the RNA polymerase II, which is CTK1 dependent.[1][2][3][4][5][6][7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
During mRNA elongation, the SRI domain of the histone H3 methyltransferase Set2 binds to the phosphorylated carboxyl-terminal domain (CTD) of RNA polymerase II. The solution structure of the yeast Set2 SRI domain reveals a novel CTD-binding fold consisting of a left-handed three-helix bundle. NMR titration shows that the SRI domain binds an Ser2/Ser5-phosphorylated CTD peptide comprising two heptapeptide repeats and three flanking NH2-terminal residues, whereas a single CTD repeat is insufficient for binding. Residues that show strong chemical shift perturbations upon CTD binding cluster in two regions. Both CTD tyrosine side chains contact the SRI domain. One of the tyrosines binds in the region with the strongest chemical shift perturbations, formed by the two NH2-terminal helices. Unexpectedly, the SRI domain fold resembles the structure of an RNA polymerase-interacting domain in bacterial sigma factors (domain sigma2 in sigma70).
Structure and carboxyl-terminal domain (CTD) binding of the Set2 SRI domain that couples histone H3 Lys36 methylation to transcription.,Vojnic E, Simon B, Strahl BD, Sattler M, Cramer P J Biol Chem. 2006 Jan 6;281(1):13-5. Epub 2005 Nov 14. PMID:16286474[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
↑Strahl BD, Grant PA, Briggs SD, Sun ZW, Bone JR, Caldwell JA, Mollah S, Cook RG, Shabanowitz J, Hunt DF, Allis CD. Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression. Mol Cell Biol. 2002 Mar;22(5):1298-306. PMID:11839797
↑Xiao T, Hall H, Kizer KO, Shibata Y, Hall MC, Borchers CH, Strahl BD. Phosphorylation of RNA polymerase II CTD regulates H3 methylation in yeast. Genes Dev. 2003 Mar 1;17(5):654-63. PMID:12629047 doi:http://dx.doi.org/10.1101/gad.1055503
↑Schaft D, Roguev A, Kotovic KM, Shevchenko A, Sarov M, Shevchenko A, Neugebauer KM, Stewart AF. The histone 3 lysine 36 methyltransferase, SET2, is involved in transcriptional elongation. Nucleic Acids Res. 2003 May 15;31(10):2475-82. doi: 10.1093/nar/gkg372. PMID:12736296 doi:http://dx.doi.org/10.1093/nar/gkg372
↑Krogan NJ, Kim M, Tong A, Golshani A, Cagney G, Canadien V, Richards DP, Beattie BK, Emili A, Boone C, Shilatifard A, Buratowski S, Greenblatt J. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol Cell Biol. 2003 Jun;23(12):4207-18. doi: 10.1128/MCB.23.12.4207-4218.2003. PMID:12773564 doi:http://dx.doi.org/10.1128/MCB.23.12.4207-4218.2003
↑Landry J, Sutton A, Hesman T, Min J, Xu RM, Johnston M, Sternglanz R. Set2-catalyzed methylation of histone H3 represses basal expression of GAL4 in Saccharomyces cerevisiae. Mol Cell Biol. 2003 Sep;23(17):5972-8. doi: 10.1128/MCB.23.17.5972-5978.2003. PMID:12917322 doi:http://dx.doi.org/10.1128/MCB.23.17.5972-5978.2003
↑Kizer KO, Phatnani HP, Shibata Y, Hall H, Greenleaf AL, Strahl BD. A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation. Mol Cell Biol. 2005 Apr;25(8):3305-16. PMID:15798214 doi:http://dx.doi.org/25/8/3305
↑Rao B, Shibata Y, Strahl BD, Lieb JD. Dimethylation of histone H3 at lysine 36 demarcates regulatory and nonregulatory chromatin genome-wide. Mol Cell Biol. 2005 Nov;25(21):9447-59. PMID:16227595 doi:http://dx.doi.org/25/21/9447
↑Vojnic E, Simon B, Strahl BD, Sattler M, Cramer P. Structure and carboxyl-terminal domain (CTD) binding of the Set2 SRI domain that couples histone H3 Lys36 methylation to transcription. J Biol Chem. 2006 Jan 6;281(1):13-5. Epub 2005 Nov 14. PMID:16286474 doi:http://dx.doi.org/10.1074/jbc.C500423200
