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. 1997 Dec 15;25(24):4926–4932. doi: 10.1093/nar/25.24.4926

CDF-1-mediated repression of cell cycle genes targets a specific subset of transactivators.

J Zwicker 1, F C Lucibello 1, V Jérôme 1, S Brüsselbach 1, R Müller 1
PMCID: PMC147152  PMID: 9396798

Abstract

The cdc25C , cyclin A and cdc2 genes are regulated during the cell cycle through two contiguous repressor binding sites, the CDE and CHR, located in the region of transcription initiation and interacting with a factor termed CDF-1. The target of this repression seems to be transcriptional activation of these promoters by transcription factors bound upstream. The majority of these factors falls into the class of glutamine-rich activators, suggesting that CDF-1-mediated repression might be activation domain specific. In the present study we have used chimeric promoter constructs to demonstrate that the cdc25C UAS, but not the core promoter, is crucial for repression. In addition, we show that only specific transcription factors and activation domains are responsive to CDE-CHR-mediated cell cycle regulation. These observations clearly indicate that CDF-1 interferes with activation of transcription by a specific subset of transactivators. The repressible activation domains belong to the same class of glutamine-rich activators, pointing to specific interactions of CDF-1 with components of the transcription machinery. In agreement with this conclusion we find that a simple inversion of the CDE-CHR module completely abrogates cell cycle-regulated repression.

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Selected References

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  1. Bremner R., Cohen B. L., Sopta M., Hamel P. A., Ingles C. J., Gallie B. L., Phillips R. A. Direct transcriptional repression by pRB and its reversal by specific cyclins. Mol Cell Biol. 1995 Jun;15(6):3256–3265. doi: 10.1128/mcb.15.6.3256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bunker C. A., Kingston R. E. Transcriptional repression by Drosophila and mammalian Polycomb group proteins in transfected mammalian cells. Mol Cell Biol. 1994 Mar;14(3):1721–1732. doi: 10.1128/mcb.14.3.1721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chiang C. M., Roeder R. G. Cloning of an intrinsic human TFIID subunit that interacts with multiple transcriptional activators. Science. 1995 Jan 27;267(5197):531–536. doi: 10.1126/science.7824954. [DOI] [PubMed] [Google Scholar]
  4. Courey A. J., Tjian R. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell. 1988 Dec 2;55(5):887–898. doi: 10.1016/0092-8674(88)90144-4. [DOI] [PubMed] [Google Scholar]
  5. Courtois S. J., Lafontaine D. A., Lemaigre F. P., Durviaux S. M., Rousseau G. G. Nuclear factor-I and activator protein-2 bind in a mutually exclusive way to overlapping promoter sequences and trans-activate the human growth hormone gene. Nucleic Acids Res. 1990 Jan 11;18(1):57–64. doi: 10.1093/nar/18.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coustry F., Maity S. N., de Crombrugghe B. Studies on transcription activation by the multimeric CCAAT-binding factor CBF. J Biol Chem. 1995 Jan 6;270(1):468–475. doi: 10.1074/jbc.270.1.468. [DOI] [PubMed] [Google Scholar]
  7. Cowell I. G. Repression versus activation in the control of gene transcription. Trends Biochem Sci. 1994 Jan;19(1):38–42. doi: 10.1016/0968-0004(94)90172-4. [DOI] [PubMed] [Google Scholar]
  8. Das G., Hinkley C. S., Herr W. Basal promoter elements as a selective determinant of transcriptional activator function. Nature. 1995 Apr 13;374(6523):657–660. doi: 10.1038/374657a0. [DOI] [PubMed] [Google Scholar]
  9. Desbarats L., Gaubatz S., Eilers M. Discrimination between different E-box-binding proteins at an endogenous target gene of c-myc. Genes Dev. 1996 Feb 15;10(4):447–460. doi: 10.1101/gad.10.4.447. [DOI] [PubMed] [Google Scholar]
  10. Dikstein R., Zhou S., Tjian R. Human TAFII 105 is a cell type-specific TFIID subunit related to hTAFII130. Cell. 1996 Oct 4;87(1):137–146. doi: 10.1016/s0092-8674(00)81330-6. [DOI] [PubMed] [Google Scholar]
  11. Fondell J. D., Brunel F., Hisatake K., Roeder R. G. Unliganded thyroid hormone receptor alpha can target TATA-binding protein for transcriptional repression. Mol Cell Biol. 1996 Jan;16(1):281–287. doi: 10.1128/mcb.16.1.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ge H., Roeder R. G. Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes. Cell. 1994 Aug 12;78(3):513–523. doi: 10.1016/0092-8674(94)90428-6. [DOI] [PubMed] [Google Scholar]
  13. Good L., Nazar R. N. An improved thermal cycle for two-step PCR-based targeted mutagenesis. Nucleic Acids Res. 1992 Sep 25;20(18):4934–4934. doi: 10.1093/nar/20.18.4934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Goodrich J. A., Tjian R. TBP-TAF complexes: selectivity factors for eukaryotic transcription. Curr Opin Cell Biol. 1994 Jun;6(3):403–409. doi: 10.1016/0955-0674(94)90033-7. [DOI] [PubMed] [Google Scholar]
  15. Hagemeier C., Bannister A. J., Cook A., Kouzarides T. The activation domain of transcription factor PU.1 binds the retinoblastoma (RB) protein and the transcription factor TFIID in vitro: RB shows sequence similarity to TFIID and TFIIB. Proc Natl Acad Sci U S A. 1993 Feb 15;90(4):1580–1584. doi: 10.1073/pnas.90.4.1580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hassig C. A., Fleischer T. C., Billin A. N., Schreiber S. L., Ayer D. E. Histone deacetylase activity is required for full transcriptional repression by mSin3A. Cell. 1997 May 2;89(3):341–347. doi: 10.1016/s0092-8674(00)80214-7. [DOI] [PubMed] [Google Scholar]
  17. Hoey T., Weinzierl R. O., Gill G., Chen J. L., Dynlacht B. D., Tjian R. Molecular cloning and functional analysis of Drosophila TAF110 reveal properties expected of coactivators. Cell. 1993 Jan 29;72(2):247–260. doi: 10.1016/0092-8674(93)90664-c. [DOI] [PubMed] [Google Scholar]
  18. Hooft van Huijsduijnen R., Li X. Y., Black D., Matthes H., Benoist C., Mathis D. Co-evolution from yeast to mouse: cDNA cloning of the two NF-Y (CP-1/CBF) subunits. EMBO J. 1990 Oct;9(10):3119–3127. doi: 10.1002/j.1460-2075.1990.tb07509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Hurford R. K., Jr, Cobrinik D., Lee M. H., Dyson N. pRB and p107/p130 are required for the regulated expression of different sets of E2F responsive genes. Genes Dev. 1997 Jun 1;11(11):1447–1463. doi: 10.1101/gad.11.11.1447. [DOI] [PubMed] [Google Scholar]
  20. Johnson A. D. The price of repression. Cell. 1995 Jun 2;81(5):655–658. doi: 10.1016/0092-8674(95)90524-3. [DOI] [PubMed] [Google Scholar]
  21. Kretzschmar M., Kaiser K., Lottspeich F., Meisterernst M. A novel mediator of class II gene transcription with homology to viral immediate-early transcriptional regulators. Cell. 1994 Aug 12;78(3):525–534. doi: 10.1016/0092-8674(94)90429-4. [DOI] [PubMed] [Google Scholar]
  22. Levine M., Manley J. L. Transcriptional repression of eukaryotic promoters. Cell. 1989 Nov 3;59(3):405–408. doi: 10.1016/0092-8674(89)90024-x. [DOI] [PubMed] [Google Scholar]
  23. Li X. Y., Hooft van Huijsduijnen R., Mantovani R., Benoist C., Mathis D. Intron-exon organization of the NF-Y genes. Tissue-specific splicing modifies an activation domain. J Biol Chem. 1992 May 5;267(13):8984–8990. [PubMed] [Google Scholar]
  24. Lowings P., Yavuzer U., Goding C. R. Positive and negative elements regulate a melanocyte-specific promoter. Mol Cell Biol. 1992 Aug;12(8):3653–3662. doi: 10.1128/mcb.12.8.3653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lucibello F. C., Truss M., Zwicker J., Ehlert F., Beato M., Müller R. Periodic cdc25C transcription is mediated by a novel cell cycle-regulated repressor element (CDE). EMBO J. 1995 Jan 3;14(1):132–142. doi: 10.1002/j.1460-2075.1995.tb06983.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mantovani R., Pessara U., Tronche F., Li X. Y., Knapp A. M., Pasquali J. L., Benoist C., Mathis D. Monoclonal antibodies to NF-Y define its function in MHC class II and albumin gene transcription. EMBO J. 1992 Sep;11(9):3315–3322. doi: 10.1002/j.1460-2075.1992.tb05410.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mermod N., O'Neill E. A., Kelly T. J., Tjian R. The proline-rich transcriptional activator of CTF/NF-I is distinct from the replication and DNA binding domain. Cell. 1989 Aug 25;58(4):741–753. doi: 10.1016/0092-8674(89)90108-6. [DOI] [PubMed] [Google Scholar]
  28. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  29. Müller R. Transcriptional regulation during the mammalian cell cycle. Trends Genet. 1995 May;11(5):173–178. doi: 10.1016/S0168-9525(00)89039-3. [DOI] [PubMed] [Google Scholar]
  30. Nagy L., Kao H. Y., Chakravarti D., Lin R. J., Hassig C. A., Ayer D. E., Schreiber S. L., Evans R. M. Nuclear receptor repression mediated by a complex containing SMRT, mSin3A, and histone deacetylase. Cell. 1997 May 2;89(3):373–380. doi: 10.1016/s0092-8674(00)80218-4. [DOI] [PubMed] [Google Scholar]
  31. Pengue G., Lania L. Krüppel-associated box-mediated repression of RNA polymerase II promoters is influenced by the arrangement of basal promoter elements. Proc Natl Acad Sci U S A. 1996 Feb 6;93(3):1015–1020. doi: 10.1073/pnas.93.3.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Regier J. L., Shen F., Triezenberg S. J. Pattern of aromatic and hydrophobic amino acids critical for one of two subdomains of the VP16 transcriptional activator. Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):883–887. doi: 10.1073/pnas.90.3.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sadhu K., Reed S. I., Richardson H., Russell P. Human homolog of fission yeast cdc25 mitotic inducer is predominantly expressed in G2. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5139–5143. doi: 10.1073/pnas.87.13.5139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Salminen A., Braun T., Buchberger A., Jürs S., Winter B., Arnold H. H. Transcription of the muscle regulatory gene Myf4 is regulated by serum components, peptide growth factors and signaling pathways involving G proteins. J Cell Biol. 1991 Nov;115(4):905–917. doi: 10.1083/jcb.115.4.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sauer F., Fondell J. D., Ohkuma Y., Roeder R. G., Jäckle H. Control of transcription by Krüppel through interactions with TFIIB and TFIIE beta. Nature. 1995 May 11;375(6527):162–164. doi: 10.1038/375162a0. [DOI] [PubMed] [Google Scholar]
  36. Schreier T., Kedes L., Gahlmann R. Cloning, structural analysis, and expression of the human slow twitch skeletal muscle/cardiac troponin C gene. J Biol Chem. 1990 Dec 5;265(34):21247–21253. [PubMed] [Google Scholar]
  37. Seipel K., Georgiev O., Schaffner W. Different activation domains stimulate transcription from remote ('enhancer') and proximal ('promoter') positions. EMBO J. 1992 Dec;11(13):4961–4968. doi: 10.1002/j.1460-2075.1992.tb05603.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shibata K., Muraosa Y., Tomita Y., Tagami H., Shibahara S. Identification of a cis-acting element that enhances the pigment cell-specific expression of the human tyrosinase gene. J Biol Chem. 1992 Oct 15;267(29):20584–20588. [PubMed] [Google Scholar]
  39. Sinha S., Maity S. N., Lu J., de Crombrugghe B. Recombinant rat CBF-C, the third subunit of CBF/NFY, allows formation of a protein-DNA complex with CBF-A and CBF-B and with yeast HAP2 and HAP3. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1624–1628. doi: 10.1073/pnas.92.5.1624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Smale S. T., Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. doi: 10.1016/0092-8674(89)90176-1. [DOI] [PubMed] [Google Scholar]
  41. Thut C. J., Goodrich J. A., Tjian R. Repression of p53-mediated transcription by MDM2: a dual mechanism. Genes Dev. 1997 Aug 1;11(15):1974–1986. doi: 10.1101/gad.11.15.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Tommasi S., Pfeifer G. P. In vivo structure of the human cdc2 promoter: release of a p130-E2F-4 complex from sequences immediately upstream of the transcription initiation site coincides with induction of cdc2 expression. Mol Cell Biol. 1995 Dec;15(12):6901–6913. doi: 10.1128/mcb.15.12.6901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Urban M. B., Baeuerle P. A. The 65-kD subunit of NF-kappa B is a receptor for I kappa B and a modulator of DNA-binding specificity. Genes Dev. 1990 Nov;4(11):1975–1984. doi: 10.1101/gad.4.11.1975. [DOI] [PubMed] [Google Scholar]
  44. Webster N. J., Green S., Tasset D., Ponglikitmongkol M., Chambon P. The transcriptional activation function located in the hormone-binding domain of the human oestrogen receptor is not encoded in a single exon. EMBO J. 1989 May;8(5):1441–1446. doi: 10.1002/j.1460-2075.1989.tb03526.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Weintraub S. J., Chow K. N., Luo R. X., Zhang S. H., He S., Dean D. C. Mechanism of active transcriptional repression by the retinoblastoma protein. Nature. 1995 Jun 29;375(6534):812–815. doi: 10.1038/375812a0. [DOI] [PubMed] [Google Scholar]
  46. Wilson R. E., Dooley T. P., Hart I. R. Induction of tumorigenicity and lack of in vitro growth requirement for 12-O-tetradecanoylphorbol-13-acetate by transfection of murine melanocytes with v-Ha-ras. Cancer Res. 1989 Feb 1;49(3):711–716. [PubMed] [Google Scholar]
  47. Yaffe D., Saxel O. Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature. 1977 Dec 22;270(5639):725–727. doi: 10.1038/270725a0. [DOI] [PubMed] [Google Scholar]
  48. Zenke M., Grundström T., Matthes H., Wintzerith M., Schatz C., Wildeman A., Chambon P. Multiple sequence motifs are involved in SV40 enhancer function. EMBO J. 1986 Feb;5(2):387–397. doi: 10.1002/j.1460-2075.1986.tb04224.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Zwicker J., Gross C., Lucibello F. C., Truss M., Ehlert F., Engeland K., Müller R. Cell cycle regulation of cdc25C transcription is mediated by the periodic repression of the glutamine-rich activators NF-Y and Sp1. Nucleic Acids Res. 1995 Oct 11;23(19):3822–3830. doi: 10.1093/nar/23.19.3822. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Zwicker J., Liu N., Engeland K., Lucibello F. C., Müller R. Cell cycle regulation of E2F site occupation in vivo. Science. 1996 Mar 15;271(5255):1595–1597. doi: 10.1126/science.271.5255.1595. [DOI] [PubMed] [Google Scholar]
  51. Zwicker J., Lucibello F. C., Wolfraim L. A., Gross C., Truss M., Engeland K., Müller R. Cell cycle regulation of the cyclin A, cdc25C and cdc2 genes is based on a common mechanism of transcriptional repression. EMBO J. 1995 Sep 15;14(18):4514–4522. doi: 10.1002/j.1460-2075.1995.tb00130.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Zwicker J., Müller R. Cell-cycle regulation of gene expression by transcriptional repression. Trends Genet. 1997 Jan;13(1):3–6. doi: 10.1016/s0168-9525(96)30112-1. [DOI] [PubMed] [Google Scholar]

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