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Gene Review

SAS2  -  Sas2p

Saccharomyces cerevisiae S288c

Synonyms: ESO1, Histone acetyltransferase SAS2, Something about silencing protein 2, YM9553.03C, YMR127C
 
 
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Disease relevance of SAS2

  • Previous analysis indicated that SAS2 is homologous to a human gene that is a site of recurring translocations involved in acute myeloid leukemia [1].
 

High impact information on SAS2

  • Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin [2].
  • These data indicate that opposing effects of Sir2p and Sas2p on acetylation of H4-Lys16 maintain the boundary at telomeric heterochromatin [2].
  • The deletions of CAC1 (cac1Delta), ASF1 (asf1Delta), and SAS2 (sas2Delta) had similar effects on gene silencing and were partially overlapping [3].
  • Here we identify a ~450-kD SAS complex containing Sas2p, Sas4p, and the tf2f-related Sas5 protein [4].
  • Furthermore, Sas2 was found in a nuclear protein complex that included Sas4 and Sas5, a homolog of TAF(II)30 [3].
 

Biological context of SAS2

  • The yeast SAS2 (Something About Silencing 2) gene encodes a member of the MYST protein family of histone acetyltransferases (HATs) and is involved in transcriptional silencing at all silent loci (HML, HMR, telomeres, and rDNA) in Saccharomyces cerevisiae [5].
  • Furthermore, the observation that a mutation of H4 lysine 16 to arginine displayed the identical silencing phenotypes as sas2Delta suggested that it was the in vivo target of Sas2 acetylation [3].
  • Here, we have isolated and characterized mutations in SAS2 as second-site suppressors of the silencing defect of HMRa-e**. Silencing conferred by the removal of SAS2 (sas2 delta) depended upon the integrity of the ARS consensus sequence of the HMR-E silencer, thus arguing for an involvement of the origin recognition complex (ORC) [6].
  • Sas2 is the catalytic subunit of a yeast histone acetyltransferase complex termed SAS complex [5].
  • SAS1 and SAS2 exhibit distinct patterns of genomic organization and developmentally regulated gene expression [7].
 

Associations of SAS2 with chemical compounds

  • Mutations in the conserved acetyl-CoA binding motif of Sas2p are shown to disrupt the ability of Sas2p to mediate the silencing at HML and telomeres, providing evidence for an important role for the acetyltransferase activity of the SAS complex in silencing [4].
 

Other interactions of SAS2

  • We found that deletion of SAS2 in combination with a null allele of SIR1 changed the chromatin structure of the precisely positioned nucleosome, which includes the mRNA start site of the alpha2 gene and derepressed alpha2 transcription [8].
  • The something about silencing (Sas) 2 protein of Saccharomyces cerevisiae, a member of the MYST (MOZ, Ybf2/Sas3, Sas2, and TIP60) acetyltransferase family, promotes silencing at HML and telomeres [4].
  • Here we show that recombinant Sas2 has HAT activity that absolutely requires Sas4 and is stimulated by Sas5 [9].
  • Thus, the Sas2p and Sir2p function in concert to regulate transcription in yeast, by acetylating and deacetylating H4-Lys16 in a mechanism that may be common to all eukaryotes [10].
  • O5257 shows homology with the SAS2 protein and another hypothetical protein from yeast [11].

References

  1. Identification of SAS4 and SAS5, two genes that regulate silencing in Saccharomyces cerevisiae. Xu, E.Y., Kim, S., Replogle, K., Rine, J., Rivier, D.H. Genetics (1999) [Pubmed]
  2. Sir2p and Sas2p opposingly regulate acetylation of yeast histone H4 lysine16 and spreading of heterochromatin. Suka, N., Luo, K., Grunstein, M. Nat. Genet. (2002) [Pubmed]
  3. The silencing complex SAS-I links histone acetylation to the assembly of repressed chromatin by CAF-I and Asf1 in Saccharomyces cerevisiae. Meijsing, S.H., Ehrenhofer-Murray, A.E. Genes Dev. (2001) [Pubmed]
  4. The yeast SAS (something about silencing) protein complex contains a MYST-type putative acetyltransferase and functions with chromatin assembly factor ASF1. Osada, S., Sutton, A., Muster, N., Brown, C.E., Yates, J.R., Sternglanz, R., Workman, J.L. Genes Dev. (2001) [Pubmed]
  5. Characterization of the yeast trimeric-SAS acetyltransferase complex. Shia, W.J., Osada, S., Florens, L., Swanson, S.K., Washburn, M.P., Workman, J.L. J. Biol. Chem. (2005) [Pubmed]
  6. The role of Sas2, an acetyltransferase homologue of Saccharomyces cerevisiae, in silencing and ORC function. Ehrenhofer-Murray, A.E., Rivier, D.H., Rine, J. Genetics (1997) [Pubmed]
  7. SAS1 and SAS2, GTP-binding protein genes in Dictyostelium discoideum with sequence similarities to essential genes in Saccharomyces cerevisiae. Saxe, S.A., Kimmel, A.R. Mol. Cell. Biol. (1990) [Pubmed]
  8. Chromatin assembly factor Asf1p-dependent occupancy of the SAS histone acetyltransferase complex at the silent mating-type locus HMLalpha. Osada, S., Kurita, M., Nishikawa, J., Nishihara, T. Nucleic Acids Res. (2005) [Pubmed]
  9. Sas4 and Sas5 are required for the histone acetyltransferase activity of Sas2 in the SAS complex. Sutton, A., Shia, W.J., Band, D., Kaufman, P.D., Osada, S., Workman, J.L., Sternglanz, R. J. Biol. Chem. (2003) [Pubmed]
  10. Chromosomal gradient of histone acetylation established by Sas2p and Sir2p functions as a shield against gene silencing. Kimura, A., Umehara, T., Horikoshi, M. Nat. Genet. (2002) [Pubmed]
  11. Sequence and analysis of a 26.9 kb fragment from chromosome XV of the yeast Saccharomyces cerevisiae. Boyer, J., Michaux, G., Fairhead, C., Gaillon, L., Dujon, B. Yeast (1996) [Pubmed]
 
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