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GCN5  -  histone acetyltransferase GCN5

Saccharomyces cerevisiae S288c

Synonyms: AAS104, ADA4, Histone acetyltransferase GCN5, SWI9, YGR252W
 
 
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Disease relevance of GCN5

 

High impact information on GCN5

  • Here we show that stable promoter occupancy by SWI/SNF and SAGA in the absence of transcription activators requires the bromodomains of the Swi2/Snf2 and Gcn5 subunits, respectively, and nucleosome acetylation [4].
  • The bromodomain in the Spt7 subunit of SAGA is dispensable for this activity but will anchor SAGA if it is swapped into Gcn5, indicating that specificity of bromodomain function is determined in part by the subunit it occupies [4].
  • Surprisingly, prearresting cells in late mitosis imposes a requirement for SWI/SNF in recruiting Gcn5p HAT activity to the GAL1 promoter, and GAL1 expression also becomes dependent on both chromatin remodeling enzymes [5].
  • Regulation of eukaryotic gene expression requires ATP-dependent chromatin remodeling enzymes, such as SWI/SNF, and histone acetyltransferases, such as Gcn5p [5].
  • We propose that SWI/SNF and Gcn5p are globally required for mitotic gene expression due to the condensed state of mitotic chromatin [5].
 

Biological context of GCN5

  • Further, the combined loss of GCN5 and SAS3 functions results in an extensive, global loss of H3 acetylation and arrest in the G(2)/M phase of the cell cycle [6].
  • This suggests that ADA2 and GCN5 are part of a heteromeric complex that mediates transcriptional activation [7].
  • Finally, we examine dependence on GCN5 and SWI-SNF at two model promoters and find that although these two chromatin-remodeling and/or modification activities may sometimes work together, in other instances they act in complementary fashion [8].
  • The yeast GCN5 gene encodes the catalytic subunit of a nuclear histone acetyltransferase and is part of a high-molecular-weight complex involved in transcriptional regulation [9].
  • These results indicate that GCN5 can contribute to chromatin remodeling at activator binding sites and that dependence on coactivator function for a given activator can vary according to the type and strength of contacts that it makes with other factors [8].
 

Associations of GCN5 with chemical compounds

  • The deletion of GCN5 markedly reduced the PR and NER of UV-induced cyclobutane pyrimidine dimers in MFA2 but much less so in RPB2, whereas no detectable defect was seen for repair of the genome overall [10].
  • GCN5 is required for activation upon adenine limitation by Bas1p/Bas2p [11].
  • The coactivator p/CIP/SRC-3 facilitates retinoic acid receptor signaling via recruitment of GCN5 [12].
  • Swi/SNF-GCN5-dependent chromatin remodelling determines induced expression of GDH3, one of the paralogous genes responsible for ammonium assimilation and glutamate biosynthesis in Saccharomyces cerevisiae [13].
  • Both normal and polyglutamine- expanded ataxin-7 are components of TFTC-type GCN5 histone acetyltransferase- containing complexes [14].
 

Physical interactions of GCN5

 

Enzymatic interactions of GCN5

  • Snf1 can phosphorylate recombinant Gcn5 in vitro [16].
  • The anti-silencing effect of Gcn5p is abolished by a mutation that eliminated its HAT activity or by deleting the ADA2 gene encoding a structural component of Gcn5p-containing HAT complexes [18].
 

Regulatory relationships of GCN5

  • In this paper we show that full activation of the HO promoter in vivo requires the Gcn5 protein and that defects in this protein can be suppressed by deletion of the RPD3 gene, which encodes a histone deacetylase [9].
  • A deletion of only the Ada2 SANT domain has exactly the same effect, strongly suggesting that Ada2 controls Gcn5 activity by virtue of its SANT domain [19].
  • We have investigated the role of the HAT Gcn5 at the nucleosomally regulated PHO5 promoter [20].
  • Microarray experiments did not reveal a close correspondence between those genes activated by Gcn4p and genes requiring the H3 or H4 tail, and analysis of published microarray data indicates that Gcn4p-regulated genes are not in general strongly dependent on Gcn5p [21].
  • However, fusion of SUMO to the N-terminus of Gcn5 to mimic constitutive sumoylation resulted in defective growth on 3-aminotriazole media and reduced basal and activated transcription of the SAGA-dependent gene TRP3 [22].
 

Other interactions of GCN5

  • Simultaneous disruption of SAS3, the homolog of the MOZ leukemia gene, and GCN5, the hGCN5/PCAF homolog, is synthetically lethal due to loss of acetyltransferase activity [6].
  • Here we show that even though the steady-state level of activated PHO5 transcription is not affected by deletion of GCN5, the rate of activation following phosphate starvation is significantly decreased [23].
  • These and other results suggest that Gcn5 and Rpd3 play distinct roles, modulating transcription initiation in opposite directions under two different cellular conditions [24].
  • We report that Gcn5, a histone H3 acetylase, plays a central role in initiation of meiosis via effects on IME2 expression [24].
  • We show here that mutations in ADA2, ADA3, and GCN5, which are believed to encode subunits of a nuclear histone acetyltransferase complex, cause phenotypes strikingly similar to that of swi/snf mutants [25].
 

Analytical, diagnostic and therapeutic context of GCN5

  • We propose a model in which the ADA/GCN5 and SWI/SNF complexes facilitate activator function by acting in concert to disrupt or modify chromatin structure [25].
  • Gel-filtration chromatography revealed two populations of GCN5 with Stokes' radii of 67 and 33 A, consistent with a large macromolecular complex and a monomer, respectively [26].
  • Chromatin immunoprecipitation experiments show decreased binding of TBP to promoters in mot1 mutants and a further decrease when combined with either nhp6ab or gcn5 mutations [27].
  • By a combination of mass spectrometry analysis and immunoblotting, we demonstrate that the adapter proteins Ada2, Ada3, and Gcn5 are indeed integral components of ADA [28].
  • Sequence alignment shows significant similarity of Nut1 to the GCN5-related N-acetyltransferase superfamily [29].

References

  1. Crystal structure of a GCN5-related N-acetyltransferase: Serratia marcescens aminoglycoside 3-N-acetyltransferase. Wolf, E., Vassilev, A., Makino, Y., Sali, A., Nakatani, Y., Burley, S.K. Cell (1998) [Pubmed]
  2. Stimulation of DNA replication from the polyomavirus origin by PCAF and GCN5 acetyltransferases: acetylation of large T antigen. Xie, A.Y., Bermudez, V.P., Folk, W.R. Mol. Cell. Biol. (2002) [Pubmed]
  3. Adenovirus E1A requires the yeast SAGA histone acetyltransferase complex and associates with SAGA components Gcn5 and Tra1. Kulesza, C.A., Van Buskirk, H.A., Cole, M.D., Reese, J.C., Smith, M.M., Engel, D.A. Oncogene (2002) [Pubmed]
  4. Function and selectivity of bromodomains in anchoring chromatin-modifying complexes to promoter nucleosomes. Hassan, A.H., Prochasson, P., Neely, K.E., Galasinski, S.C., Chandy, M., Carrozza, M.J., Workman, J.L. Cell (2002) [Pubmed]
  5. Global role for chromatin remodeling enzymes in mitotic gene expression. Krebs, J.E., Fry, C.J., Samuels, M.L., Peterson, C.L. Cell (2000) [Pubmed]
  6. Histone H3 specific acetyltransferases are essential for cell cycle progression. Howe, L., Auston, D., Grant, P., John, S., Cook, R.G., Workman, J.L., Pillus, L. Genes Dev. (2001) [Pubmed]
  7. Functional similarity and physical association between GCN5 and ADA2: putative transcriptional adaptors. Marcus, G.A., Silverman, N., Berger, S.L., Horiuchi, J., Guarente, L. EMBO J. (1994) [Pubmed]
  8. GCN5 dependence of chromatin remodeling and transcriptional activation by the GAL4 and VP16 activation domains in budding yeast. Stafford, G.A., Morse, R.H. Mol. Cell. Biol. (2001) [Pubmed]
  9. Mutations in chromatin components suppress a defect of Gcn5 protein in Saccharomyces cerevisiae. Pérez-Martín, J., Johnson, A.D. Mol. Cell. Biol. (1998) [Pubmed]
  10. The Saccharomyces cerevisiae histone acetyltransferase Gcn5 has a role in the photoreactivation and nucleotide excision repair of UV-induced cyclobutane pyrimidine dimers in the MFA2 gene. Teng, Y., Yu, Y., Waters, R. J. Mol. Biol. (2002) [Pubmed]
  11. Nucleosome position-dependent and -independent activation of HIS7 epression in Saccharomyces cerevisiae by different transcriptional activators. Valerius, O., Brendel, C., Wagner, C., Krappmann, S., Thoma, F., Braus, G.H. Eukaryotic Cell (2003) [Pubmed]
  12. The coactivator p/CIP/SRC-3 facilitates retinoic acid receptor signaling via recruitment of GCN5. Brown, K., Chen, Y., Underhill, T.M., Mymryk, J.S., Torchia, J. J. Biol. Chem. (2003) [Pubmed]
  13. Swi/SNF-GCN5-dependent chromatin remodelling determines induced expression of GDH3, one of the paralogous genes responsible for ammonium assimilation and glutamate biosynthesis in Saccharomyces cerevisiae. Avendaño, A., Riego, L., DeLuna, A., Aranda, C., Romero, G., Ishida, C., Vázquez-Acevedo, M., Rodarte, B., Recillas-Targa, F., Valenzuela, L., Zonszein, S., González, A. Mol. Microbiol. (2005) [Pubmed]
  14. Both normal and polyglutamine- expanded ataxin-7 are components of TFTC-type GCN5 histone acetyltransferase- containing complexes. Helmlinger, D., Hardy, S., Eberlin, A., Devys, D., Tora, L. Biochem. Soc. Symp. (2006) [Pubmed]
  15. Global histone acetylation and deacetylation in yeast. Vogelauer, M., Wu, J., Suka, N., Grunstein, M. Nature (2000) [Pubmed]
  16. Histone H3 Ser10 phosphorylation-independent function of Snf1 and Reg1 proteins rescues a gcn5- mutant in HIS3 expression. Liu, Y., Xu, X., Singh-Rodriguez, S., Zhao, Y., Kuo, M.H. Mol. Cell. Biol. (2005) [Pubmed]
  17. ADA1, a novel component of the ADA/GCN5 complex, has broader effects than GCN5, ADA2, or ADA3. Horiuchi, J., Silverman, N., Piña, B., Marcus, G.A., Guarente, L. Mol. Cell. Biol. (1997) [Pubmed]
  18. A targeted histone acetyltransferase can create a sizable region of hyperacetylated chromatin and counteract the propagation of transcriptionally silent chromatin. Chiu, Y.H., Yu, Q., Sandmeier, J.J., Bi, X. Genetics (2003) [Pubmed]
  19. Multiple mechanistically distinct functions of SAGA at the PHO5 promoter. Barbaric, S., Reinke, H., Hörz, W. Mol. Cell. Biol. (2003) [Pubmed]
  20. Absence of Gcn5 HAT activity defines a novel state in the opening of chromatin at the PHO5 promoter in yeast. Gregory, P.D., Schmid, A., Zavari, M., Lui, L., Berger, S.L., Hörz, W. Mol. Cell (1998) [Pubmed]
  21. Contribution of the histone H3 and H4 amino termini to Gcn4p- and Gcn5p-mediated transcription in yeast. Yu, C., Palumbo, M.J., Lawrence, C.E., Morse, R.H. J. Biol. Chem. (2006) [Pubmed]
  22. Sumoylation of the yeast Gcn5 protein. Sterner, D.E., Nathan, D., Reindle, A., Johnson, E.S., Berger, S.L. Biochemistry (2006) [Pubmed]
  23. Increasing the rate of chromatin remodeling and gene activation--a novel role for the histone acetyltransferase Gcn5. Barbaric, S., Walker, J., Schmid, A., Svejstrup, J.Q., Hörz, W. EMBO J. (2001) [Pubmed]
  24. GCN5-dependent histone H3 acetylation and RPD3-dependent histone H4 deacetylation have distinct, opposing effects on IME2 transcription, during meiosis and during vegetative growth, in budding yeast. Burgess, S.M., Ajimura, M., Kleckner, N. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  25. Role for ADA/GCN5 products in antagonizing chromatin-mediated transcriptional repression. Pollard, K.J., Peterson, C.L. Mol. Cell. Biol. (1997) [Pubmed]
  26. Human histone acetyltransferase GCN5 exists in a stable macromolecular complex lacking the adapter ADA2. Forsberg, E.C., Lam, L.T., Yang, X.J., Nakatani, Y., Bresnick, E.H. Biochemistry (1997) [Pubmed]
  27. Genetic interactions between Nhp6 and Gcn5 with Mot1 and the Ccr4-Not complex that regulate binding of TATA-binding protein in Saccharomyces cerevisiae. Biswas, D., Yu, Y., Mitra, D., Stillman, D.J. Genetics (2006) [Pubmed]
  28. The ADA complex is a distinct histone acetyltransferase complex in Saccharomyces cerevisiae. Eberharter, A., Sterner, D.E., Schieltz, D., Hassan, A., Yates, J.R., Berger, S.L., Workman, J.L. Mol. Cell. Biol. (1999) [Pubmed]
  29. Mediator-nucleosome interaction. Lorch, Y., Beve, J., Gustafsson, C.M., Myers, L.C., Kornberg, R.D. Mol. Cell (2000) [Pubmed]
 
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