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. 1997 Dec 15;25(24):4915–4920. doi: 10.1093/nar/25.24.4915

CDF-1, a novel E2F-unrelated factor, interacts with cell cycle-regulated repressor elements in multiple promoters.

N Liu 1, F C Lucibello 1, K Körner 1, L A Wolfraim 1, J Zwicker 1, R Müller 1
PMCID: PMC147142  PMID: 9396796

Abstract

The cdc25C , cdc2 and cyclin A promoters are controlled by transcriptional repression through two contiguous protein binding sites, termed the CDE and CHR. In the present study we have identified a factor, CDF-1, which interacts with the cdc25C CDE-CHR module. CDF-1 binds to the CDE in the major groove and to the CHR in the minor grove in a cooperative fashion in vitro , in a manner similar to that seen by genomic footprinting. In agreement with in vivo binding data and its putative function as a periodic repressor, DNA binding by CDF-1 in nuclear extracts is down-regulated during cell cycle progression. CDF-1 also binds avidly to the CDE-CHR modules of the cdc2 and cyclin A promoters, but not to the E2F site in the B- myb promoter. Conversely, E2F complexes do not recognize the cdc25C CDE-CHR and CDF-1 is immunologically unrelated to all known E2F and DP family members. This indicates that E2F- and CDF-mediated repression is controlled by different factors acting at different stages during the cell cycle. While E2F-mediated repression seems to be associated with genes that are up-regulated early (around mid G1), such as B- myb , CDE-CHR-controlled genes, such as cdc25C , cdc2 and cyclin A , become derepressed later. Finally, the fractionation of native nuclear extracts on glycerol gradients leads to separation of CDF-1 from both E2F complexes and pocket proteins of the pRb family. This emphasizes the conclusion that CDF-1 is not an E2F family member and points to profound differences in the cell cycle regulation of CDF-1 and E2F.

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Selected References

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  1. Bennett J. D., Farlie P. G., Watson R. J. E2F binding is required but not sufficient for repression of B-myb transcription in quiescent fibroblasts. Oncogene. 1996 Sep 5;13(5):1073–1082. [PubMed] [Google Scholar]
  2. 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]
  3. Helin K., Ed H. The retinoblastoma protein as a transcriptional repressor. Trends Cell Biol. 1993 Feb;3(2):43–46. doi: 10.1016/0962-8924(93)90150-y. [DOI] [PubMed] [Google Scholar]
  4. Hsiao K. M., McMahon S. L., Farnham P. J. Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. Genes Dev. 1994 Jul 1;8(13):1526–1537. doi: 10.1101/gad.8.13.1526. [DOI] [PubMed] [Google Scholar]
  5. Huet X., Rech J., Plet A., Vié A., Blanchard J. M. Cyclin A expression is under negative transcriptional control during the cell cycle. Mol Cell Biol. 1996 Jul;16(7):3789–3798. doi: 10.1128/mcb.16.7.3789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Johnson D. G., Ohtani K., Nevins J. R. Autoregulatory control of E2F1 expression in response to positive and negative regulators of cell cycle progression. Genes Dev. 1994 Jul 1;8(13):1514–1525. doi: 10.1101/gad.8.13.1514. [DOI] [PubMed] [Google Scholar]
  7. Klehr D., Maass K., Bode J. Scaffold-attached regions from the human interferon beta domain can be used to enhance the stable expression of genes under the control of various promoters. Biochemistry. 1991 Feb 5;30(5):1264–1270. doi: 10.1021/bi00219a015. [DOI] [PubMed] [Google Scholar]
  8. La Thangue N. B. E2F and the molecular mechanisms of early cell-cycle control. Biochem Soc Trans. 1996 Feb;24(1):54–59. doi: 10.1042/bst0240054. [DOI] [PubMed] [Google Scholar]
  9. Lam E. W., Watson R. J. An E2F-binding site mediates cell-cycle regulated repression of mouse B-myb transcription. EMBO J. 1993 Jul;12(7):2705–2713. doi: 10.1002/j.1460-2075.1993.tb05932.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Liu N., Lucibello F. C., Zwicker J., Engeland K., Müller R. Cell cycle-regulated repression of B-myb transcription: cooperation of an E2F site with a contiguous corepressor element. Nucleic Acids Res. 1996 Aug 1;24(15):2905–2910. doi: 10.1093/nar/24.15.2905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Ohtani K., DeGregori J., Leone G., Herendeen D. R., Kelly T. J., Nevins J. R. Expression of the HsOrc1 gene, a human ORC1 homolog, is regulated by cell proliferation via the E2F transcription factor. Mol Cell Biol. 1996 Dec;16(12):6977–6984. doi: 10.1128/mcb.16.12.6977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pfeifer G. P., Steigerwald S. D., Mueller P. R., Wold B., Riggs A. D. Genomic sequencing and methylation analysis by ligation mediated PCR. Science. 1989 Nov 10;246(4931):810–813. doi: 10.1126/science.2814502. [DOI] [PubMed] [Google Scholar]
  15. Sellers W. R., Rodgers J. W., Kaelin W. G., Jr A potent transrepression domain in the retinoblastoma protein induces a cell cycle arrest when bound to E2F sites. Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11544–11548. doi: 10.1073/pnas.92.25.11544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shelby R. D., Vafa O., Sullivan K. F. Assembly of CENP-A into centromeric chromatin requires a cooperative array of nucleosomal DNA contact sites. J Cell Biol. 1997 Feb 10;136(3):501–513. doi: 10.1083/jcb.136.3.501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Uchiumi T., Longo D. L., Ferris D. K. Cell cycle regulation of the human polo-like kinase (PLK) promoter. J Biol Chem. 1997 Apr 4;272(14):9166–9174. doi: 10.1074/jbc.272.14.9166. [DOI] [PubMed] [Google Scholar]
  18. Weinberg R. A. The retinoblastoma protein and cell cycle control. Cell. 1995 May 5;81(3):323–330. doi: 10.1016/0092-8674(95)90385-2. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Weintraub S. J., Prater C. A., Dean D. C. Retinoblastoma protein switches the E2F site from positive to negative element. Nature. 1992 Jul 16;358(6383):259–261. doi: 10.1038/358259a0. [DOI] [PubMed] [Google Scholar]
  21. Zamanian M., La Thangue N. B. Transcriptional repression by the Rb-related protein p107. Mol Biol Cell. 1993 Apr;4(4):389–396. doi: 10.1091/mbc.4.4.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Zhu L., Zhu L., Xie E., Chang L. S. Differential roles of two tandem E2F sites in repression of the human p107 promoter by retinoblastoma and p107 proteins. Mol Cell Biol. 1995 Jul;15(7):3552–3562. doi: 10.1128/mcb.15.7.3552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. 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]
  26. 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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