The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

SET2  -  Set2p

Saccharomyces cerevisiae S288c

Synonyms: EZL1, Histone-lysine N-methyltransferase, H3 lysine-36 specific, J0520, KMT3, Lysine N-methyltransferase 3, ...
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

High impact information on SET2

  • These results suggest that the conformational state of P38, controlled by Fpr4, is important for methylation of H3K36 by Set2 [1].
  • Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex [2].
  • Chromatin immunoprecipitation and biochemical experiments indicate that the chromodomain of Eaf3 recruits Rpd3C(S) to nucleosomes methylated by Set2 on histone H3 lysine 36, leading to deacetylation of transcribed regions [2].
  • This pathway apparently acts to negatively regulate transcription because deleting the genes for Set2 or Rpd3C(S) bypasses the requirement for the positive elongation factor Bur1/Bur2 [2].
  • Rpd3C(S) mutants exhibit phenotypes remarkably similar to those of Set2, a histone methyltransferase associated with elongating RNA polymerase II [2].
 

Biological context of SET2

  • We further show that lysine 36 of histone H3 at GAL4 is methylated and that this methylation is dependent upon the presence of SET2 [3].
  • In agreement with this, we have determined that deletion of SET2, its SRI domain, or amino acid substitutions at K36 result in an alteration of RNAPII occupancy levels over transcribing genes [4].
  • These data indicate that Pol II-associated Set2 methylates H3 providing a transcriptional memory which signals for deacetylation of ORFs by Rpd3S [5].
  • Furthermore, yeast strains carrying set2 alleles that are catalytically inactive or yeast strains bearing point mutations at K36 were also found to be resistant to 6AU [4].
  • A set2 deletion results in slight sensitivity to 6-azauracil and much less beta-galactosidase produced by a reporter plasmid, resulting from a defect in transcription [6].
 

Associations of SET2 with chemical compounds

  • Conversion of lysine 36 to an unmethylatable arginine causes a decrease in the repression of GAL4 transcription, as does a Delta set2 mutation [3].
  • Unexpectedly, BIACORE analysis reveals that the SRI domain binds specifically, and with high affinity, to CTD repeats that are doubly modified (serine 2 and serine 5 phosphorylated), indicating that Set2 association across the body of genes requires a specific pattern of phosphorylated RNAPII [4].
 

Enzymatic interactions of SET2

  • Third, the association of SET2 with CTD phosphorylated RPO21 remained in the absence of ssn3 [7].
 

Other interactions of SET2

  • Second, all of the co-purifying RNAP II subunit, RPO21, was phosphorylated at serines 5 and 2 of the C-terminal domain (CTD) tail, indicating that the SET2 association is specific to either the elongating or SSN3 repressed forms (or both) of RNAP II [7].
  • Fourth, in the absence of ssn3, mRNA production from gal1 required SET2 [7].
  • The BUR1 cyclin-dependent protein kinase is required for the normal pattern of histone methylation by SET2 [8].
  • Deletions of three yeast genes, SET2, CDC73, and DST1, involved in transcriptional elongation and/or chromatin metabolism were used in conjunction with genetic array technology to screen approximately 4700 yeast deletions and identify double deletion mutants that produce synthetic growth defects [9].
  • Deletion of CTK1, encoding an RNAPII CTD kinase, prevents Lys36 methylation and Set2 recruitment, suggesting that methylation may be triggered by contact of the WW domain or C terminus of Set2 with Ser2-phosphorylated CTD [6].
 

Analytical, diagnostic and therapeutic context of SET2

References

  1. Proline isomerization of histone h3 regulates lysine methylation and gene expression. Nelson, C.J., Santos-Rosa, H., Kouzarides, T. Cell (2006) [Pubmed]
  2. Cotranscriptional set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Keogh, M.C., Kurdistani, S.K., Morris, S.A., Ahn, S.H., Podolny, V., Collins, S.R., Schuldiner, M., Chin, K., Punna, T., Thompson, N.J., Boone, C., Emili, A., Weissman, J.S., Hughes, T.R., Strahl, B.D., Grunstein, M., Greenblatt, J.F., Buratowski, S., Krogan, N.J. Cell (2005) [Pubmed]
  3. Set2-catalyzed methylation of histone H3 represses basal expression of GAL4 in Saccharomyces cerevisiae. Landry, J., Sutton, A., Hesman, T., Min, J., Xu, R.M., Johnston, M., Sternglanz, R. Mol. Cell. Biol. (2003) [Pubmed]
  4. A novel domain in Set2 mediates RNA polymerase II interaction and couples histone H3 K36 methylation with transcript elongation. Kizer, K.O., Phatnani, H.P., Shibata, Y., Hall, H., Greenleaf, A.L., Strahl, B.D. Mol. Cell. Biol. (2005) [Pubmed]
  5. Histone H3 methylation by Set2 directs deacetylation of coding regions by Rpd3S to suppress spurious intragenic transcription. Carrozza, M.J., Li, B., Florens, L., Suganuma, T., Swanson, S.K., Lee, K.K., Shia, W.J., Anderson, S., Yates, J., Washburn, M.P., Workman, J.L. Cell (2005) [Pubmed]
  6. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Krogan, N.J., Kim, M., Tong, A., Golshani, A., Cagney, G., Canadien, V., Richards, D.P., Beattie, B.K., Emili, A., Boone, C., Shilatifard, A., Buratowski, S., Greenblatt, J. Mol. Cell. Biol. (2003) [Pubmed]
  7. The histone 3 lysine 36 methyltransferase, SET2, is involved in transcriptional elongation. Schaft, D., Roguev, A., Kotovic, K.M., Shevchenko, A., Sarov, M., Shevchenko, A., Neugebauer, K.M., Stewart, A.F. Nucleic Acids Res. (2003) [Pubmed]
  8. The BUR1 cyclin-dependent protein kinase is required for the normal pattern of histone methylation by SET2. Chu, Y., Sutton, A., Sternglanz, R., Prelich, G. Mol. Cell. Biol. (2006) [Pubmed]
  9. A Snf2 family ATPase complex required for recruitment of the histone H2A variant Htz1. Krogan, N.J., Keogh, M.C., Datta, N., Sawa, C., Ryan, O.W., Ding, H., Haw, R.A., Pootoolal, J., Tong, A., Canadien, V., Richards, D.P., Wu, X., Emili, A., Hughes, T.R., Buratowski, S., Greenblatt, J.F. Mol. Cell (2003) [Pubmed]
  10. The Set2 histone methyltransferase functions through the phosphorylated carboxyl-terminal domain of RNA polymerase II. Li, B., Howe, L., Anderson, S., Yates, J.R., Workman, J.L. J. Biol. Chem. (2003) [Pubmed]
 
WikiGenes - Universities