Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter.
10.1101/gad.8.13.1526
Crossref journal-article
Cold Spring Harbor Laboratory
Genes & Development (246)
Abstract

To prepare for the DNA synthesis (S) phase of the cell cycle, transcription of many genes required for nucleotide biosynthesis increases. The promoters of several of these genes contain binding sites for the E2F family of transcription factors, and, in many cases, mutation of these sites abolishes growth-regulated transcription. The RNA levels of one family member, E2F1, increase about 15-fold at the G1/S-phase boundary and expression of E2F1 in quiescent cells activates transcription from some G1/S-phase-specific promoters, suggesting that E2F1 plays a critical role in preparing cells to enter S phase. To elucidate the signal transduction pathway leading to the activation of genes required for DNA synthesis, we are investigating the mechanism by which expression of E2F1 is regulated. To determine whether levels of E2F1 mRNA are controlled by changes in promoter activity, we have cloned and characterized the mouse E2F1 promoter. Sequence analysis revealed two sets of overlapping E2F-binding sites located between -12 and -40 relative to the transcription initiation site. We show that these sites bind cellular E2F and that an E2F1 promoter fragment can be activated up to 100-fold by coexpression of E2F proteins. We also show that the activity of this E2F1 promoter fragment increases approximately 80-fold at the G1/S-phase boundary and that this activation is, in part, regulated by G0-specific repression via the E2F sites. However, the E2F sites are not sufficient to mediate growth-regulated transcriptional activity; our results indicate that multiple DNA elements are required for transcription regulation of the E2F1 promoter at the G1/S-phase boundary.

Bibliography

Hsiao, K. M., McMahon, S. L., & Farnham, P. J. (1994). Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter. Genes & Development, 8(13), 1526–1537.

Authors 3
  1. K M Hsiao (first)
  2. S L McMahon (additional)
  3. P J Farnham (additional)
References 47 Referenced 191
  1. 10.1038/352249a0
  2. 10.1002/j.1460-2075.1993.tb06116.x / EMBO J. / Functional synergy between DP-1 and E2F-1 in the cell cycle-regulating transcription factor DRTF1/E2F. (1993)
  3. 10.1038/355176a0
  4. {'key': '2021111418160541000_8.13.1526.4', 'first-page': '3975', 'article-title': 'Cell cycle analysis of E2F in primary human T cells reveals novel E2F complexes and biochemically distinct forms of free E2F.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Cell cycle analysis of E2F in primary human T cells reveals novel E2F complexes and biochemically distinct forms of free E2F. (1993)
  5. 10.1002/j.1460-2075.1992.tb05231.x / EMBO J. / Cell cycle regulation of the human cdc2 gene. (1992)
  6. 10.1016/0092-8674(92)90215-X
  7. 10.1093/nar/11.5.1475
  8. 10.1016/S0021-9258(17)42259-9 / J. Biol. Chem. / G1/S-regulated E2F-containing protein complexes bind to the mouse thymidine kinase gene promoter. (1994)
  9. {'key': '2021111418160541000_8.13.1526.9', 'first-page': '179', 'article-title': 'Characterization of the 5′ end of the growth-regulated Syrian hamster CAD gene.', 'volume': '1', 'year': '1990', 'journal-title': 'Cell & Growth Differ.'} / Cell & Growth Differ. / Characterization of the 5′ end of the growth-regulated Syrian hamster CAD gene. (1990)
  10. {'key': '2021111418160541000_8.13.1526.10', 'first-page': '125', 'article-title': 'The role of E2F in the mammalian cell cycle.', 'volume': '1155', 'year': '1993', 'journal-title': 'Biochim. Biophys. Acta'} / Biochim. Biophys. Acta / The role of E2F in the mammalian cell cycle. (1993)
  11. 10.1038/362083a0
  12. 10.1093/nar/21.22.4998
  13. {'key': '2021111418160541000_8.13.1526.13', 'first-page': '3431', 'article-title': 'Transcriptional repression of the E2-containing promoters EIIaE, c-myc, and RB1 by the product of the RB1 gene.', 'volume': '8', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Transcriptional repression of the E2-containing promoters EIIaE, c-myc, and RB1 by the product of the RB1 gene. (1992)
  14. 10.1016/0092-8674(92)90107-N
  15. 10.1101/gad.7.10.1850
  16. 10.1016/0092-8674(93)90664-C
  17. {'key': '2021111418160541000_8.13.1526.17', 'first-page': '7802', 'article-title': 'Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F. (1993)
  18. 10.1073/pnas.87.12.4732
  19. 10.1038/365349a0
  20. 10.1016/0092-8674(92)90108-O
  21. {'key': '2021111418160541000_8.13.1526.21', 'first-page': '2455', 'article-title': 'The retinoblastoma gene product regulates Sp1-mediated transcription.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The retinoblastoma gene product regulates Sp1-mediated transcription. (1992)
  22. 10.1126/science.8248803
  23. 10.1002/j.1460-2075.1993.tb05932.x / EMBO J. / An E2F-binding site mediates cell-cycle regulated repression of mouse B-myb transcription. (1993)
  24. 10.1073/pnas.90.13.6145
  25. 10.1101/gad.6.10.1874
  26. 10.1128/MCB.13.12.7813
  27. 10.1073/pnas.90.8.3554
  28. 10.1016/0092-8674(91)90467-D
  29. {'key': '2021111418160541000_8.13.1526.29', 'first-page': '1861', 'article-title': 'Cloning, chromosomal location, and characterization of mouse E2F1.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Cloning, chromosomal location, and characterization of mouse E2F1. (1994)
  30. {'key': '2021111418160541000_8.13.1526.30', 'first-page': '2599', 'article-title': 'The hsp70 gene CCAAT-binding factor mediates transcriptional activation by the adenovirus E1A protein.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The hsp70 gene CCAAT-binding factor mediates transcriptional activation by the adenovirus E1A protein. (1992)
  31. Maniatis, T., E.F. Fritsch, and J. Sambrook. 1982. Molecular cloning: A laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York.
  32. 10.1073/pnas.88.13.5670
  33. {'key': '2021111418160541000_8.13.1526.33', 'first-page': '653', 'article-title': 'Transcription initiation from the dihydrofolate reductase promoter is positioned by HIP1 binding at the initiation site.', 'volume': '10', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Transcription initiation from the dihydrofolate reductase promoter is positioned by HIP1 binding at the initiation site. (1990)
  34. {'key': '2021111418160541000_8.13.1526.34', 'first-page': '1054', 'article-title': 'The HIP1 binding site is required for growth regulation of the dihydrofolate reductase gene promoter.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The HIP1 binding site is required for growth regulation of the dihydrofolate reductase gene promoter. (1992)
  35. 10.1016/S0021-9258(18)82309-2 / J. Biol. Chem. / An inhibitory raf-1 mutant suppresses expression of a subset of v-raf-activated genes. (1993)
  36. 10.1016/0092-8674(91)90019-U
  37. 10.1126/science.1411535
  38. {'key': '2021111418160541000_8.13.1526.38', 'first-page': '1681', 'article-title': 'Binding of the human E2F transcription factor to the retinoblastoma protein but not to cyclin A is abolished in HPV-16-immortalized cells.', 'volume': '7', 'year': '1992', 'journal-title': 'Oncogene'} / Oncogene / Binding of the human E2F transcription factor to the retinoblastoma protein but not to cyclin A is abolished in HPV-16-immortalized cells. (1992)
  39. 10.1016/S0021-9258(18)53860-6 / J. Biol. Chem. / A specific CCAAT-binding protein, CBP/tk, may be involved in the regulation of thymidine kinase gene expression in human IMR-90 diploid fibroblasts during senescence. (1993)
  40. {'key': '2021111418160541000_8.13.1526.40', 'first-page': '2081', 'article-title': 'Human DNA polymerase α gene: Sequences controlling expression in cycling and serum-stimulated cells.', 'volume': '11', 'year': '1991', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Human DNA polymerase α gene: Sequences controlling expression in cycling and serum-stimulated cells. (1991)
  41. {'key': '2021111418160541000_8.13.1526.41', 'first-page': '299', 'article-title': 'The transcription factor E2F-1 mediates the autoregulation of RB gene expression.', 'volume': '14', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / The transcription factor E2F-1 mediates the autoregulation of RB gene expression. (1994)
  42. {'key': '2021111418160541000_8.13.1526.42', 'first-page': '5620', 'article-title': 'Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: Identification of a gene with properties of the transcription factor E2F.', 'volume': '12', 'year': '1992', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: Identification of a gene with properties of the transcription factor E2F. (1992)
  43. 10.1016/0092-8674(92)90214-W
  44. {'key': '2021111418160541000_8.13.1526.44', 'first-page': '1610', 'article-title': 'A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter.', 'volume': '13', 'year': '1993', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / A protein synthesis-dependent increase in E2F1 mRNA correlates with growth regulation of the dihydrofolate reductase promoter. (1993)
  45. 10.1073/pnas.90.8.3265
  46. 10.1038/358259a0
  47. 10.1016/S0021-9258(19)50002-3 / J. Biol. Chem. / The retinoblastoma gene product suppresses neu oncogene-induced transformation via transcriptional repression of neu*. (1992)
Dates
Type When
Created 18 years, 2 months ago (June 5, 2007, 5:15 p.m.)
Deposited 3 years, 9 months ago (Nov. 14, 2021, 9:21 p.m.)
Indexed 2 months, 2 weeks ago (June 11, 2025, 5:29 a.m.)
Issued 31 years, 1 month ago (July 1, 1994)
Published 31 years, 1 month ago (July 1, 1994)
Published Online 31 years, 1 month ago (July 1, 1994)
Published Print 31 years, 1 month ago (July 1, 1994)
Funders 0

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@article{Hsiao_1994, title={Multiple DNA elements are required for the growth regulation of the mouse E2F1 promoter.}, volume={8}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.8.13.1526}, DOI={10.1101/gad.8.13.1526}, number={13}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Hsiao, K M and McMahon, S L and Farnham, P J}, year={1994}, month=jul, pages={1526–1537} }