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. 1998 Jun 15;26(12):2948–2954. doi: 10.1093/nar/26.12.2948

Cloning of Drosophila GCN5: conserved features among metazoan GCN5 family members.

E R Smith 1, J M Belote 1, R L Schiltz 1, X J Yang 1, P A Moore 1, S L Berger 1, Y Nakatani 1, C D Allis 1
PMCID: PMC147644  PMID: 9611240

Abstract

PCAF and hGCN5 are distinct human genes that encode proteins related to the yeast histone acetyltransferase and transcriptional adapter GCN5. The PCAF protein shares extensive similarity with the 439 amino acids of yGCN5, but it has an approximately 350 amino acid N-terminal extension that interacts with the transcriptional co-activator p300/CBP. Adenoviral protein E1a can disrupt PCAF-CBP interactions and prevent PCAF-dependent cellular differentiation. In this report, we describe the cloning and initial characterization of a Drosophila homolog of yGCN5. In addition to the homology to yGCN5, the Drosophila protein shares sequencesimilarity with the N-terminal portion of human PCAF that is involved in binding to CBP. In the course of characterizing dGCN5, we have discovered that hGCN5 also contains an N-terminal extension with significant similarity to PCAF. Interestingly, in the case of the h GCN5 gene, alternative splicing may regulate the production of full-length hGCN5. The presence of the N-terminal domain in a Drosophila GCN5 homolog and both human homologs suggests that it was part of the ancestral form of metazoan GCN5.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akimaru H., Chen Y., Dai P., Hou D. X., Nonaka M., Smolik S. M., Armstrong S., Goodman R. H., Ishii S. Drosophila CBP is a co-activator of cubitus interruptus in hedgehog signalling. Nature. 1997 Apr 17;386(6626):735–738. doi: 10.1038/386735a0. [DOI] [PubMed] [Google Scholar]
  2. Bannister A. J., Kouzarides T. The CBP co-activator is a histone acetyltransferase. Nature. 1996 Dec 19;384(6610):641–643. doi: 10.1038/384641a0. [DOI] [PubMed] [Google Scholar]
  3. Barlev N. A., Poltoratsky V., Owen-Hughes T., Ying C., Liu L., Workman J. L., Berger S. L. Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex. Mol Cell Biol. 1998 Mar;18(3):1349–1358. doi: 10.1128/mcb.18.3.1349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berger S. L., Piña B., Silverman N., Marcus G. A., Agapite J., Regier J. L., Triezenberg S. J., Guarente L. Genetic isolation of ADA2: a potential transcriptional adaptor required for function of certain acidic activation domains. Cell. 1992 Jul 24;70(2):251–265. doi: 10.1016/0092-8674(92)90100-q. [DOI] [PubMed] [Google Scholar]
  5. Bone J. R., Lavender J., Richman R., Palmer M. J., Turner B. M., Kuroda M. I. Acetylated histone H4 on the male X chromosome is associated with dosage compensation in Drosophila. Genes Dev. 1994 Jan;8(1):96–104. doi: 10.1101/gad.8.1.96. [DOI] [PubMed] [Google Scholar]
  6. Borrow J., Stanton V. P., Jr, Andresen J. M., Becher R., Behm F. G., Chaganti R. S., Civin C. I., Disteche C., Dubé I., Frischauf A. M. The translocation t(8;16)(p11;p13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet. 1996 Sep;14(1):33–41. doi: 10.1038/ng0996-33. [DOI] [PubMed] [Google Scholar]
  7. Brownell J. E., Zhou J., Ranalli T., Kobayashi R., Edmondson D. G., Roth S. Y., Allis C. D. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell. 1996 Mar 22;84(6):843–851. doi: 10.1016/s0092-8674(00)81063-6. [DOI] [PubMed] [Google Scholar]
  8. Candau R., Moore P. A., Wang L., Barlev N., Ying C. Y., Rosen C. A., Berger S. L. Identification of human proteins functionally conserved with the yeast putative adaptors ADA2 and GCN5. Mol Cell Biol. 1996 Feb;16(2):593–602. doi: 10.1128/mcb.16.2.593. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Candau R., Zhou J. X., Allis C. D., Berger S. L. Histone acetyltransferase activity and interaction with ADA2 are critical for GCN5 function in vivo. EMBO J. 1997 Feb 3;16(3):555–565. doi: 10.1093/emboj/16.3.555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chen H., Lin R. J., Schiltz R. L., Chakravarti D., Nash A., Nagy L., Privalsky M. L., Nakatani Y., Evans R. M. Nuclear receptor coactivator ACTR is a novel histone acetyltransferase and forms a multimeric activation complex with P/CAF and CBP/p300. Cell. 1997 Aug 8;90(3):569–580. doi: 10.1016/s0092-8674(00)80516-4. [DOI] [PubMed] [Google Scholar]
  11. Currie R. A. NF-Y is associated with the histone acetyltransferases GCN5 and P/CAF. J Biol Chem. 1998 Jan 16;273(3):1430–1434. doi: 10.1074/jbc.273.3.1430. [DOI] [PubMed] [Google Scholar]
  12. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Du W., Vidal M., Xie J. E., Dyson N. RBF, a novel RB-related gene that regulates E2F activity and interacts with cyclin E in Drosophila. Genes Dev. 1996 May 15;10(10):1206–1218. doi: 10.1101/gad.10.10.1206. [DOI] [PubMed] [Google Scholar]
  14. Dynlacht B. D., Brook A., Dembski M., Yenush L., Dyson N. DNA-binding and trans-activation properties of Drosophila E2F and DP proteins. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6359–6363. doi: 10.1073/pnas.91.14.6359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ernst R. K., Bray M., Rekosh D., Hammarskjöld M. L. A structured retroviral RNA element that mediates nucleocytoplasmic export of intron-containing RNA. Mol Cell Biol. 1997 Jan;17(1):135–144. doi: 10.1128/mcb.17.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Forsberg E. C., Lam L. T., Yang X. J., Nakatani Y., Bresnick E. H. Human histone acetyltransferase GCN5 exists in a stable macromolecular complex lacking the adapter ADA2. Biochemistry. 1997 Dec 16;36(50):15918–15924. doi: 10.1021/bi971664x. [DOI] [PubMed] [Google Scholar]
  17. Georgakopoulos T., Thireos G. Two distinct yeast transcriptional activators require the function of the GCN5 protein to promote normal levels of transcription. EMBO J. 1992 Nov;11(11):4145–4152. doi: 10.1002/j.1460-2075.1992.tb05507.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Grunstein M. Histone acetylation in chromatin structure and transcription. Nature. 1997 Sep 25;389(6649):349–352. doi: 10.1038/38664. [DOI] [PubMed] [Google Scholar]
  19. Haynes S. R., Dollard C., Winston F., Beck S., Trowsdale J., Dawid I. B. The bromodomain: a conserved sequence found in human, Drosophila and yeast proteins. Nucleic Acids Res. 1992 May 25;20(10):2603–2603. doi: 10.1093/nar/20.10.2603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kamei Y., Xu L., Heinzel T., Torchia J., Kurokawa R., Gloss B., Lin S. C., Heyman R. A., Rose D. W., Glass C. K. A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell. 1996 May 3;85(3):403–414. doi: 10.1016/s0092-8674(00)81118-6. [DOI] [PubMed] [Google Scholar]
  21. Katzen A. L., Kornberg T. B., Bishop J. M. Isolation of the proto-oncogene c-myb from D. melanogaster. Cell. 1985 Jun;41(2):449–456. doi: 10.1016/s0092-8674(85)80018-0. [DOI] [PubMed] [Google Scholar]
  22. Korzus E., Torchia J., Rose D. W., Xu L., Kurokawa R., McInerney E. M., Mullen T. M., Glass C. K., Rosenfeld M. G. Transcription factor-specific requirements for coactivators and their acetyltransferase functions. Science. 1998 Jan 30;279(5351):703–707. doi: 10.1126/science.279.5351.703. [DOI] [PubMed] [Google Scholar]
  23. Kuo M. H., Brownell J. E., Sobel R. E., Ranalli T. A., Cook R. G., Edmondson D. G., Roth S. Y., Allis C. D. Transcription-linked acetylation by Gcn5p of histones H3 and H4 at specific lysines. Nature. 1996 Sep 19;383(6597):269–272. doi: 10.1038/383269a0. [DOI] [PubMed] [Google Scholar]
  24. Kuo M. H., Zhou J., Jambeck P., Churchill M. E., Allis C. D. Histone acetyltransferase activity of yeast Gcn5p is required for the activation of target genes in vivo. Genes Dev. 1998 Mar 1;12(5):627–639. doi: 10.1101/gad.12.5.627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lustig K. D., Kirschner M. W. Use of an oocyte expression assay to reconstitute inductive signaling. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6234–6238. doi: 10.1073/pnas.92.14.6234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maruyama I. N., Rakow T. L., Maruyama H. I. cRACE: a simple method for identification of the 5' end of mRNAs. Nucleic Acids Res. 1995 Sep 25;23(18):3796–3797. doi: 10.1093/nar/23.18.3796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mizzen C. A., Yang X. J., Kokubo T., Brownell J. E., Bannister A. J., Owen-Hughes T., Workman J., Wang L., Berger S. L., Kouzarides T. The TAF(II)250 subunit of TFIID has histone acetyltransferase activity. Cell. 1996 Dec 27;87(7):1261–1270. doi: 10.1016/s0092-8674(00)81821-8. [DOI] [PubMed] [Google Scholar]
  28. Nanbru C., Lafon I., Audigier S., Gensac M. C., Vagner S., Huez G., Prats A. C. Alternative translation of the proto-oncogene c-myc by an internal ribosome entry site. J Biol Chem. 1997 Dec 19;272(51):32061–32066. doi: 10.1074/jbc.272.51.32061. [DOI] [PubMed] [Google Scholar]
  29. O'Connell P. O., Rosbash M. Sequence, structure, and codon preference of the Drosophila ribosomal protein 49 gene. Nucleic Acids Res. 1984 Jul 11;12(13):5495–5513. doi: 10.1093/nar/12.13.5495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ogryzko V. V., Schiltz R. L., Russanova V., Howard B. H., Nakatani Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 1996 Nov 29;87(5):953–959. doi: 10.1016/s0092-8674(00)82001-2. [DOI] [PubMed] [Google Scholar]
  31. Peters C. W., Sippel A. E., Vingron M., Klempnauer K. H. Drosophila and vertebrate myb proteins share two conserved regions, one of which functions as a DNA-binding domain. EMBO J. 1987 Oct;6(10):3085–3090. doi: 10.1002/j.1460-2075.1987.tb02616.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Petrij F., Giles R. H., Dauwerse H. G., Saris J. J., Hennekam R. C., Masuno M., Tommerup N., van Ommen G. J., Goodman R. H., Peters D. J. Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. Nature. 1995 Jul 27;376(6538):348–351. doi: 10.1038/376348a0. [DOI] [PubMed] [Google Scholar]
  33. Puri P. L., Sartorelli V., Yang X. J., Hamamori Y., Ogryzko V. V., Howard B. H., Kedes L., Wang J. Y., Graessmann A., Nakatani Y. Differential roles of p300 and PCAF acetyltransferases in muscle differentiation. Mol Cell. 1997 Dec;1(1):35–45. doi: 10.1016/s1097-2765(00)80005-2. [DOI] [PubMed] [Google Scholar]
  34. Spencer T. E., Jenster G., Burcin M. M., Allis C. D., Zhou J., Mizzen C. A., McKenna N. J., Onate S. A., Tsai S. Y., Tsai M. J. Steroid receptor coactivator-1 is a histone acetyltransferase. Nature. 1997 Sep 11;389(6647):194–198. doi: 10.1038/38304. [DOI] [PubMed] [Google Scholar]
  35. Tanaka Y., Naruse I., Maekawa T., Masuya H., Shiroishi T., Ishii S. Abnormal skeletal patterning in embryos lacking a single Cbp allele: a partial similarity with Rubinstein-Taybi syndrome. Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10215–10220. doi: 10.1073/pnas.94.19.10215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Walker W. H., Girardet C., Habener J. F. Alternative exon splicing controls a translational switch from activator to repressor isoforms of transcription factor CREB during spermatogenesis. J Biol Chem. 1996 Aug 16;271(33):20145–21050. [PubMed] [Google Scholar]
  37. Wang L., Liu L., Berger S. L. Critical residues for histone acetylation by Gcn5, functioning in Ada and SAGA complexes, are also required for transcriptional function in vivo. Genes Dev. 1998 Mar 1;12(5):640–653. doi: 10.1101/gad.12.5.640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wickens M., Stephenson P. Role of the conserved AAUAAA sequence: four AAUAAA point mutants prevent messenger RNA 3' end formation. Science. 1984 Nov 30;226(4678):1045–1051. doi: 10.1126/science.6208611. [DOI] [PubMed] [Google Scholar]
  39. Wu C. Chromatin remodeling and the control of gene expression. J Biol Chem. 1997 Nov 7;272(45):28171–28174. doi: 10.1074/jbc.272.45.28171. [DOI] [PubMed] [Google Scholar]
  40. Yang X. J., Ogryzko V. V., Nishikawa J., Howard B. H., Nakatani Y. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature. 1996 Jul 25;382(6589):319–324. doi: 10.1038/382319a0. [DOI] [PubMed] [Google Scholar]
  41. Zhang J., Maquat L. E. Evidence that translation reinitiation abrogates nonsense-mediated mRNA decay in mammalian cells. EMBO J. 1997 Feb 17;16(4):826–833. doi: 10.1093/emboj/16.4.826. [DOI] [PMC free article] [PubMed] [Google Scholar]

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