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Gene Review

SET1  -  Set1p

Saccharomyces cerevisiae S288c

Synonyms: COMPASS component SET1, Histone-lysine N-methyltransferase, H3 lysine-4 specific, KMT2, Lysine N-methyltransferase 2, SET domain-containing protein 1, ...
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Disease relevance of SET1

  • Taken together, our findings suggest that SET1 regulates multiple processes important to the pathogenesis of candidiasis [1].

High impact information on SET1


Chemical compound and disease context of SET1


Biological context of SET1

  • Finally, deletion of MEC3 results in telomere elongation, whereas cells with deletions of both SET1 and MEC3 do not have elongated telomeres [3].
  • Deletion of SET1 increases the viability of mec3delta mutants after DNA damage (in a process that is mostly independent of Rad53p kinase, which has a central role in checkpoint control) but does not significantly affect cell-cycle progression [3].
  • Our findings indicate that interactions between SET1 and MEC3 have a role in DNA repair and telomere function [3].
  • With this antiserum, we show that deletion of SET1, but not of other putative SET domain-containing genes, in S. cerevisiae, results in the complete abolishment of H3 Lys4 methylation in vivo [4].
  • Inactivation of the SET1 gene in a diploid leads to a sporulation defect [5].

Anatomical context of SET1

  • Disruption of SET1 resulted in complete loss of methylation of histone 3 at lysine residue 4, hyperfilamentous growth under embedded conditions, less negative cell surface charges and diminished adherence to epithelial cells, effects that were reversed upon gene re-insertion at a disrupted locus [1].
  • A Set1 complex of reduced mass persists in murine embryonic stem cells lacking CFP1 [6].

Associations of SET1 with chemical compounds

  • Set1 association depends upon the TFIIH-associated kinase that phosphorylates the Pol II C-terminal domain (CTD) and mediates the transition between initiation and elongation, and Set1 interacts with the form of Pol II whose CTD is phosphorylated at serine 5 but not serine 2 [7].

Physical interactions of SET1

  • Methylation of histone H3 on lysines 4 and 79, catalyzed by the Set1-containing complex COMPASS and Dot1p, respectively, is required for silencing of expression of genes located near chromosome telomeres in yeast [8].

Regulatory relationships of SET1

  • We show here that H3 lysine 4 methylation also negatively regulated gene expression, as strains without Set1 showed enhanced expression of PHO5, wherein chromatin structure plays an important transcriptional regulatory role [9].

Other interactions of SET1

  • We confirmed this hypothesis by testing C. elegans homologs of three yeast genes which are established modifiers of the yeast telomeric chromatin structure (SIR2, SET1, and RAD17) for their influence on repeat-dependent transgene silencing for C. elegans [10].
  • The Spp1 subunit of complex associated with Set1 (COMPASS) and Set2, determining K4me3 and K36me2/3, respectively, are required for transient NuA4-dependent H4K8ac [11].
  • Trimethylation requires histone H2B ubiquitylation and the PAF1 complex, which are linked to transcription elongation, but how they activate Set1 is not known [12].
  • Swd2, an essential WD repeat protein in Saccharomyces cerevisiae, is a component of two very different complexes: the cleavage and polyadenylation factor CPF and the Set1 methylase, which modifies lysine 4 of histone H3 (H3-K4) [13].
  • Synthetic genetic array (SGA) and transcription microarray analyses of a BUR2 mutant revealed that BUR is functionally similar to the PAF, Rad6, and Set1 complexes [14].

Analytical, diagnostic and therapeutic context of SET1


  1. Candida albicans SET1 encodes a histone 3 lysine 4 methyltransferase that contributes to the pathogenesis of invasive candidiasis. Raman, S.B., Nguyen, M.H., Zhang, Z., Cheng, S., Jia, H.Y., Weisner, N., Iczkowski, K., Clancy, C.J. Mol. Microbiol. (2006) [Pubmed]
  2. The Set1 methyltransferase opposes Ipl1 aurora kinase functions in chromosome segregation. Zhang, K., Lin, W., Latham, J.A., Riefler, G.M., Schumacher, J.M., Chan, C., Tatchell, K., Hawke, D.H., Kobayashi, R., Dent, S.Y. Cell (2005) [Pubmed]
  3. Interaction between Set1p and checkpoint protein Mec3p in DNA repair and telomere functions. Corda, Y., Schramke, V., Longhese, M.P., Smokvina, T., Paciotti, V., Brevet, V., Gilson, E., Géli, V. Nat. Genet. (1999) [Pubmed]
  4. Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae. Briggs, S.D., Bryk, M., Strahl, B.D., Cheung, W.L., Davie, J.K., Dent, S.Y., Winston, F., Allis, C.D. Genes Dev. (2001) [Pubmed]
  5. Set1 is required for meiotic S-phase onset, double-strand break formation and middle gene expression. Sollier, J., Lin, W., Soustelle, C., Suhre, K., Nicolas, A., Géli, V., de La Roche Saint-André, C. EMBO J. (2004) [Pubmed]
  6. CpG-binding protein (CXXC finger protein 1) is a component of the mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue of the yeast Set1/COMPASS complex. Lee, J.H., Skalnik, D.G. J. Biol. Chem. (2005) [Pubmed]
  7. Targeted recruitment of Set1 histone methylase by elongating Pol II provides a localized mark and memory of recent transcriptional activity. Ng, H.H., Robert, F., Young, R.A., Struhl, K. Mol. Cell (2003) [Pubmed]
  8. The Paf1 complex is required for histone H3 methylation by COMPASS and Dot1p: linking transcriptional elongation to histone methylation. Krogan, N.J., Dover, J., Wood, A., Schneider, J., Heidt, J., Boateng, M.A., Dean, K., Ryan, O.W., Golshani, A., Johnston, M., Greenblatt, J.F., Shilatifard, A. Mol. Cell (2003) [Pubmed]
  9. Effectors of lysine 4 methylation of histone H3 in Saccharomyces cerevisiae are negative regulators of PHO5 and GAL1-10. Carvin, C.D., Kladde, M.P. J. Biol. Chem. (2004) [Pubmed]
  10. Telomeric position effect variegation in Saccharomyces cerevisiae by Caenorhabditis elegans linker histones suggests a mechanistic connection between germ line and telomeric silencing. Jedrusik, M.A., Schulze, E. Mol. Cell. Biol. (2003) [Pubmed]
  11. Dynamic lysine methylation on histone H3 defines the regulatory phase of gene transcription. Morillon, A., Karabetsou, N., Nair, A., Mellor, J. Mol. Cell (2005) [Pubmed]
  12. Histone trimethylation by Set1 is coordinated by the RRM, autoinhibitory, and catalytic domains. Schlichter, A., Cairns, B.R. EMBO J. (2005) [Pubmed]
  13. The essential WD repeat protein Swd2 has dual functions in RNA polymerase II transcription termination and lysine 4 methylation of histone H3. Cheng, H., He, X., Moore, C. Mol. Cell. Biol. (2004) [Pubmed]
  14. BUR kinase selectively regulates H3 K4 trimethylation and H2B ubiquitylation through recruitment of the PAF elongation complex. Laribee, R.N., Krogan, N.J., Xiao, T., Shibata, Y., Hughes, T.R., Greenblatt, J.F., Strahl, B.D. Curr. Biol. (2005) [Pubmed]
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