Sibling rivalry in the E2F family (original) (raw)

• Sherr, C. J. & Roberts, J. M. CDK inhibitors: positive and negative regulators of G1-phase progression. Genes Dev. 13, 1501–1512 (1999).
  Article CAS PubMed Google Scholar
• Nevins, J. R. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 258, 424–429 (1992).
  Article CAS PubMed Google Scholar
• Dyson, N. The regulation of E2F by pRB-family proteins. Genes Dev. 12, 2245–2262 (1998).
  Article CAS PubMed Google Scholar
• La Thangue, N. B. & Rigby, P. W. An adenovirus E1A-like transcription factor is regulated during the differentiation of murine embryonal carcinoma stem cells. Cell 49, 507–513 (1987).
  Article CAS PubMed Google Scholar
• Bandara, L. R. & La Thangue, N. B. Adenovirus E1a prevents the retinoblastoma gene product from complexing with a cellular transcription factor. Nature 351, 494–497 (1991).
  Article CAS PubMed Google Scholar
• Girling, R. et al. A new component of the transcription factor DRTF1/E2F. Nature 362, 83–87 (1993).
  Article CAS PubMed Google Scholar
• Weinberg, R. A. The retinoblastoma gene and gene product. Cancer Surv. 12, 43–57 (1992).
  CAS PubMed Google Scholar
• DeGregori, J., Leone, G., Ohtani, K., Miron, A. & Nevins, J. R. E2F-1 accumulation bypasses a G1 arrest resulting from the inhibition of G1 cyclin-dependent kinase activity. Genes Dev. 9, 2873–2887 (1995).
  Article CAS PubMed Google Scholar
• Schwarz, J. K. et al. Expression of the E2F1 transcription factor overcomes type-β transforming growth factor-mediated growth suppression. Proc. Natl Acad. Sci. USA 92, 483–487 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Mann, D. J. & Jones, N. C. E2F-1 but not E2F-4 can overcome p16-induced G1 cell-cycle arrest. Curr. Biol. 6, 474–483 (1996).
  Article CAS PubMed Google Scholar
• Bartek, J., Bartkova, J. & Lukas, J. The retinoblastoma protein pathway and the restriction point. Curr. Opin. Cell Biol. 8, 805–814 (1996).
  Article CAS PubMed Google Scholar
• Sherr, C. J. Cancer cell cycles. Science 274, 1672–1677 (1996).
  Article CAS PubMed Google Scholar
• Mulligan, G. & Jacks, T. The retinoblastoma gene family: cousins with overlapping interests. Trends Genet. 14, 223–229 (1998).
  Article CAS PubMed Google Scholar
• Hu, N. et al. Heterozygous Rb-1 delta 20/+ mice are predisposed to tumors of the pituitary gland with a nearly complete penetrance. Oncogene 9, 1021–1027 (1994).
  CAS PubMed Google Scholar
• Williams, B. O., Morgenbesser, S. D., DePinho, R. A. & Jacks, T. Tumorigenic and developmental effects of combined germ-line mutations in Rb and p53. Cold Spring Harb. Symp. Quant. Biol. 59, 449–457 (1994).
  Article CAS PubMed Google Scholar
• Clarke, A. R. et al. Requirement for a functional Rb-1 gene in murine development. Nature 359, 328–330 (1992).
  Article CAS PubMed Google Scholar
• Jacks, T. et al. Effects of an Rb mutation in the mouse. Nature 359, 295–300 (1992).
  Article CAS PubMed Google Scholar
• Lee, E. Y. et al. Mice deficient for Rb are nonviable and show defects in neurogenesis and haematopoiesis. Nature 359, 288–294 (1992).
  Article CAS PubMed Google Scholar
• Helin, K. et al. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F. Cell 70, 337–350 (1992).
  Article CAS PubMed Google Scholar
• Flemington, E. K., Speck, S. H. & Kaelin, W. G. Jr. E2F-1-mediated transactivation is inhibited by complex formation with the retinoblastoma susceptibility gene product. Proc. Natl Acad. Sci. USA 90, 6914–6918 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Helin, K., Harlow, E. & Fattaey, A. Inhibition of E2F-1 transactivation by direct binding of the retinoblastoma protein. Mol. Cell. Biol. 13, 6501–6508 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, H. S. & Dean, D. C. Rb-mediated chromatin structure regulation and transcriptional repression. Oncogene 20, 3134–3138 (2001).
  Article CAS PubMed Google Scholar
• Brehm, A. et al. Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391, 597–601 (1998).
  Article CAS PubMed Google Scholar
• Luo, R. X., Postigo, A. A. & Dean, D. C. Rb interacts with histone deacetylase to repress transcription. Cell 92, 463–473 (1998).
  Article CAS PubMed Google Scholar
• Chen, T. T. & Wang, J. Y. Establishment of irreversible growth arrest in myogenic differentiation requires the RB LXCXE-binding function. Mol. Cell. Biol. 20, 5571–5580 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Dahiya, A., Gavin, M. R., Luo, R. X. & Dean, D. C. Role of the LXCXE binding site in Rb function. Mol. Cell. Biol. 20, 6799–6805 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Strobeck, M. W. et al. BRG-1 is required for RB-mediated cell cycle arrest. Proc. Natl Acad. Sci. USA 97, 7748–7753 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, H. S. et al. Exit from G1 and S phase of the cell cycle is regulated by repressor complexes containing HDAC–Rb–hSWI/SNF and Rb–hSWI/SNF. Cell 101, 79–89 (2000).
  Article CAS PubMed Google Scholar
• Nielsen, S. J. et al. Rb targets histone H3 methylation and HP1 to promoters. Nature 412, 561–565 (2001).This study shows that pRB associates with both SUV39H1 and HP1 through its pocket domain. SUV39H1 cooperates with pRB in the transcriptional repression of the E2F-responsive cyclin E promoter. Moreover, in vivo ChIP assays show that HP1 is recruited to the cyclin E promoter in a pRB-dependent manner.
  Article CAS PubMed Google Scholar
• Vandel, L. et al. Transcriptional repression by the retinoblastoma protein through the recruitment of a histone methyltransferase. Mol. Cell. Biol. 21, 6484–6494 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Harbour, J. W. & Dean, D. C. The Rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev. 14, 2393–2409 (2000).
  Article CAS PubMed Google Scholar
• Bannister, A. J. et al. Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromodomain. Nature 410, 120–124 (2001).
  Article CAS PubMed Google Scholar
• Lachner, M., O'Carroll, D., Rea, S., Mechtler, K. & Jenuwein, T. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410, 116–120 (2001).
  Article CAS PubMed Google Scholar
• Helin, K. Regulation of cell proliferation by the E2F transcription factors. Curr. Opin. Genet. Dev. 8, 28–35 (1998).
  Article CAS PubMed Google Scholar
• Bandara, L. R., Buck, V. M., Zamanian, M., Johnston, L. H. & La Thangue, N. B. Functional synergy between DP-1 and E2F-1 in the cell cycle-regulating transcription factor DRTF1/E2F. EMBO J. 12, 4317–4324 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Helin, K. et al. Heterodimerization of the transcription factors E2F-1 and DP-1 leads to cooperative _trans_-activation. Genes Dev. 7, 1850–1861 (1993).
  Article CAS PubMed Google Scholar
• Krek, W., Livingston, D. M. & Shirodkar, S. Binding to DNA and the retinoblastoma gene product promoted by complex formation of different E2F family members. Science 262, 1557–1560 (1993).
  Article CAS PubMed Google Scholar
• Wu, C. L., Zukerberg, L. R., Ngwu, C., Harlow, E. & Lees, J. A. In vivo association of E2F and DP family proteins. Mol. Cell. Biol. 15, 2536–2546 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Trimarchi, J. M. et al. E2F-6, a member of the E2F family that can behave as a transcriptional repressor. Proc. Natl Acad. Sci. USA 95, 2850–2855 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Takahashi, Y., Rayman, J. B. & Dynlacht, B. D. Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression. Genes Dev. 14, 804–816 (2000).This study uses in vivo ChIP assays to examine the cell-cycle-dependent association of individual E2F and pocket proteins with several E2F-responsive promoters. In G0/G1, these promoters are primarily occupied by E2F4, p107 and p130. As cells enter late G1, there is a significant reduction in the binding of these proteins and E2F1, E2F2 and E2F3 now associate. There was no detectable difference in the spectrum of E2Fs at individual responsive genes, which indicates that they could all be regulated similarly.
  CAS PubMed PubMed Central Google Scholar
• Wells, J., Boyd, K. E., Fry, C. J., Bartley, S. M. & Farnham, P. J. Target gene specificity of E2F and pocket protein family members in living cells. Mol. Cell. Biol. 20, 5797–5807 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Kaelin, W. G. Jr et al. Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell 70, 351–364 (1992).
  Article CAS PubMed Google Scholar
• Shan, B. et al. Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F. Mol. Cell. Biol. 12, 5620–5631 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Ivey-Hoyle, M. et al. Cloning and characterization of E2F-2, a novel protein with the biochemical properties of transcription factor E2F. Mol. Cell. Biol. 13, 7802–7812 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Lees, J. A. et al. The retinoblastoma protein binds to a family of E2F transcription factors. Mol. Cell. Biol. 13, 7813–7825 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• Leone, G. et al. Identification of a novel E2F3 product suggests a mechanism for determining specificity of repression by Rb proteins. Mol. Cell. Biol. 20, 3626–3632 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Johnson, D. G., Schwarz, J. K., Cress, W. D. & Nevins, J. R. Expression of transcription factor E2F1 induces quiescent cells to enter S phase. Nature 365, 349–352 (1993).
  Article CAS PubMed Google Scholar
• Qin, X. Q., Livingston, D. M., Kaelin, W. G. Jr & Adams, P. D. Deregulated transcription factor E2F-1 expression leads to S-phase entry and p53-mediated apoptosis. Proc. Natl Acad. Sci. USA 91, 10918–10922 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Lukas, J., Petersen, B. O., Holm, K., Bartek, J. & Helin, K. Deregulated expression of E2F family members induces S-phase entry and overcomes p16INK4A-mediated growth suppression. Mol. Cell. Biol. 16, 1047–1057 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Johnson, D. G., Cress, W. D., Jakoi, L. & Nevins, J. R. Oncogenic capacity of the E2F1 gene. Proc. Natl Acad. Sci. USA 91, 12823–12827 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Shan, B. & Lee, W. H. Deregulated expression of E2F-1 induces S-phase entry and leads to apoptosis. Mol. Cell. Biol. 14, 8166–8173 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Singh, P., Wong, S. H. & Hong, W. Overexpression of E2F-1 in rat embryo fibroblasts leads to neoplastic transformation. EMBO J. 13, 3329–3338 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Xu, G., Livingston, D. M. & Krek, W. Multiple members of the E2F transcription factor family are the products of oncogenes. Proc. Natl Acad. Sci. USA 92, 1357–1361 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Leone, G. et al. E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Genes Dev. 12, 2120–2130 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Humbert, P. O. et al. E2f3 is critical for normal cellular proliferation. Genes Dev. 14, 690–703 (2000).This study shows that E2F3 acts in a dose-dependent manner to mediate the mitogen-induced activation of almost all known E2F-responsive genes. As a result, E2F3 controls the rate of proliferation of both primary and transformed MEFs.
  CAS PubMed PubMed Central Google Scholar
• Wu, L. et al. The E2F1–3 transcription factors are essential for cellular proliferation. Nature 414, 457–462 (2001).Using the conditional mutant E2f alleles, the authors show that the combined loss of E2F1, E2F2 and E2F3 completely blocks the proliferation of MEFs. This is accompanied by an increase in the levels of the Cdk inhibitor p21.
  Article CAS PubMed Google Scholar
• Wu, X. & Levine, A. J. p53 and E2F-1 cooperate to mediate apoptosis. Proc. Natl Acad. Sci. USA 91, 3602–3606 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Hiebert, S. W. et al. E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis. Mol. Cell. Biol. 15, 6864–6874 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Hsieh, J. K., Fredersdorf, S., Kouzarides, T., Martin, K. & Lu, X. E2F1-induced apoptosis requires DNA binding but not transactivation and is inhibited by the retinoblastoma protein through direct interaction. Genes Dev. 11, 1840–1852 (1997).
  Article CAS PubMed Google Scholar
• Phillips, A. C., Bates, S., Ryan, K. M., Helin, K. & Vousden, K. H. Induction of DNA synthesis and apoptosis are separable functions of E2F-1. Genes Dev. 11, 1853–1863 (1997).
  Article CAS PubMed Google Scholar
• Phillips, A. C., Ernst, M. K., Bates, S., Rice, N. R. & Vousden, K. H. E2F-1 potentiates cell death by blocking antiapoptotic signaling pathways. Mol. Cell 4, 771–781 (1999).
  Article CAS PubMed Google Scholar
• DeGregori, J., Leone, G., Miron, A., Jakoi, L. & Nevins, J. R. Distinct roles for E2F proteins in cell growth control and apoptosis. Proc. Natl Acad. Sci. USA 94, 7245–7250 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Bates, S. et al. p14ARF links the tumour suppressors RB and p53. Nature 395, 124–125 (1998).
  Article CAS PubMed Google Scholar
• Tolbert, D., Lu, X., Yin, C., Tantama, M. & Van Dyke, T. p19ARF is dispensable for oncogenic stress-induced p53-mediated apoptosis and tumor suppression in vivo. Mol. Cell. Biol. 22, 370–377 (2002).
  Article CAS PubMed PubMed Central Google Scholar
• Tsai, K. Y., MacPherson, D., Rubionson, D. A., Crowley, D., and Jacks, T. ARF is not required for apoptosis in Rb mutant mouse embryos. Curr. Biol. (in the press).
• Irwin, M. et al. Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature 407, 645–648 (2000).
  Article CAS PubMed Google Scholar
• Lissy, N. A., Davis, P. K., Irwin, M., Kaelin, W. G. & Dowdy, S. F. A common E2F-1 and p73 pathway mediates cell death induced by TCR activation. Nature 407, 642–645 (2000).
  Article CAS PubMed Google Scholar
• Stiewe, T. & Putzer, B. M. Role of the p53-homologue p73 in E2F1-induced apoptosis. Nature Genet. 26, 464–469 (2000).
  Article CAS PubMed Google Scholar
• Ishida, S. et al. Role for E2F in control of both DNA replication and mitotic functions as revealed from DNA microarray analysis. Mol. Cell. Biol. 21, 4684–4699 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Muller, H. et al. E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. Genes Dev. 15, 267–285 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Kowalik, T. F., DeGregori, J., Leone, G., Jakoi, L. & Nevins, J. R. E2F1-specific induction of apoptosis and p53 accumulation, which is blocked by Mdm2. Cell Growth Differ. 9, 113–118. (1998).
  CAS PubMed Google Scholar
• Leone, G. et al. Myc requires distinct E2F activities to induce S phase and apoptosis. Mol. Cell 8, 105–113 (2001).
  Article CAS PubMed Google Scholar
• Vigo, E. et al. CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase. Mol. Cell. Biol. 19, 6379–6395 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Tsai, K. Y. et al. Mutation of E2f-1 suppresses apoptosis and inappropriate S phase entry and extends survival of Rb-deficient mouse embryos. Mol. Cell 2, 293–304 (1998).By intercrossing the Rb and E2f1 mutant mouse strains, the authors show that E2F1 loss causes a significant reduction in the levels of ectopic S-phase entry, p53-dependent- and p53-independent-apoptosis that arises in pRB-deficient embryos. This ameliorates the defective erythropoiesis and thereby extends the lifespan of the embryo by several days.
  Article CAS PubMed Google Scholar
• Ziebold, U., Reza, T., Caron, A. & Lees, J. A. E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos. Genes Dev. 15, 386–391 (2001).This study shows that E2F3 loss almost completely suppresses the inappropriate proliferation, p53-dependent- and p53-independent-apoptosis in pRB-deficient embryos. As the degree of suppression exceeds that which results from the loss of E2F1, this indicates E2F3 can induce apoptosis in vivo independently of E2F1.
  Article CAS PubMed PubMed Central Google Scholar
• Pan, H. et al. Key roles for E2F1 in signaling p53-dependent apoptosis and in cell division within developing tumors. Mol. Cell 2, 283–292 (1998).
  Article CAS PubMed Google Scholar
• Yamasaki, L. et al. Loss of E2F-1 reduces tumorigenesis and extends the lifespan of Rb1(+/−) mice. Nature Genet. 18, 360–364 (1998).
  Article CAS PubMed Google Scholar
• Field, S. J. et al. E2F-1 functions in mice to promote apoptosis and suppress proliferation. Cell 85, 549–561 (1996).
  Article CAS PubMed Google Scholar
• Yamasaki, L. et al. Tumor induction and tissue atrophy in mice lacking E2F-1. Cell 85, 537–548 (1996).This study examines the phenotypic consequences of E2F1 deficiency. In addition to various developmental defects, the E2f1 mutant mice were unexpectedly found to have an increased susceptibility to tumours.
  Article CAS PubMed Google Scholar
• Zhu, J. W., DeRyckere, D., Li, F. X., Wan, Y. Y. & DeGregori, J. A role for E2F1 in the induction of ARF, p53, and apoptosis during thymic negative selection. Cell Growth Differ. 10, 829–838 (1999).
  CAS PubMed Google Scholar
• Garcia, I., Murga, M., Vicario, A., Field, S. J. & Zubiaga, A. M. A role for E2F1 in the induction of apoptosis during thymic negative selection. Cell Growth Differ. 11, 91–98 (2000).
  CAS PubMed Google Scholar
• Humbert, P. O. et al. E2F4 is essential for normal erythrocyte maturation and neonatal viability. Mol. Cell 6, 281–291 (2000).
  Article CAS PubMed Google Scholar
• Meng, R. D., Phillips, P. & El-Deiry, W. S. p53-independent increase in E2F-1 expression enhances the cytotoxic effects of etoposide and of adriamycin. Int. J. Oncol. 14, 5–14 (1999).
  CAS PubMed Google Scholar
• Lin, W. C., Lin, F. T. & Nevins, J. R. Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation. Genes Dev. 15, 1833–1844 (2001).
  CAS PubMed PubMed Central Google Scholar
• Maser, R. S. et al. Mre11 complex and DNA replication: linkage to E2F and sites of DNA synthesis. Mol. Cell. Biol. 21, 6006–6016 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Zhu, J. W. et al. E2F1 and E2F2 determine thresholds for antigen-induced T-cell proliferation and suppress tumorigenesis. Mol. Cell. Biol. 21, 8547–8564 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Dyson, N. et al. Analysis of p107-associated proteins: p107 associates with a form of E2F that differs from pRB-associated E2F-1. J. Virol. 67, 7641–7647 (1993).
  CAS PubMed PubMed Central Google Scholar
• Beijersbergen, R. L. et al. E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. Genes Dev. 8, 2680–2690 (1994).
  Article CAS PubMed Google Scholar
• Hijmans, E. M., Voorhoeve, P. M., Beijersbergen, R. L., van't Veer, L. J. & Bernards, R. E2F-5, a new E2F family member that interacts with p130 in vivo. Mol. Cell. Biol. 15, 3082–3089 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Vairo, G., Livingston, D. M. & Ginsberg, D. Functional interaction between E2F-4 and p130: evidence for distinct mechanisms underlying growth suppression by different retinoblastoma protein family members. Genes Dev. 9, 869–881 (1995).
  Article CAS PubMed Google Scholar
• Ikeda, M. A., Jakoi, L. & Nevins, J. R. A unique role for the Rb protein in controlling E2F accumulation during cell growth and differentiation. Proc. Natl Acad. Sci. USA 93, 3215–3220 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Moberg, K., Starz, M. A. & Lees, J. A. E2F-4 switches from p130 to p107 and pRB in response to cell-cycle re-entry. Mol. Cell. Biol. 16, 1436–1449 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Muller, H. et al. Induction of S-phase entry by E2F transcription factors depends on their nuclear localization. Mol. Cell. Biol. 17, 5508–5520 (1997).The authors show that the ability of the activating E2Fs to induce quiescent cells to re-enter the cell cycle is dependent on their nuclear localization. This is determined by a canonical basic NLS within the amino-terminal domain. By contrast, E2F4 is unable to induce cell cycle re-entry as a result of its cytoplasmic localization.
  Article CAS PubMed PubMed Central Google Scholar
• Verona, R. et al. E2F activity is regulated by cell cycle-dependent changes in subcellular localization. Mol. Cell. Biol. 17, 7268–7282 (1997).This study shows that ectopically expressed activating E2Fs are nuclear, whereas E2F4 is predominantly cytoplasmic, and the differential localization of these proteins accounts for the pronounced differences in their ability to activate transcription. It confirms that the endogenous E2F4–DP complexes are also sequestered in the cytoplasm and shows that these species become predominantly nuclear when they are bound to pRB or p130 in G0/G1. This indicates that E2F4 is primarily involved in the repression rather than the activation of E2F-responsive genes.
  Article CAS PubMed PubMed Central Google Scholar
• Magae, J., Wu, C. L., Illenye, S., Harlow, E. & Heintz, N. H. Nuclear localization of DP and E2F transcription factors by heterodimeric partners and retinoblastoma protein family members. J. Cell Sci. 109, 1717–1726 (1996).
  CAS PubMed Google Scholar
• Gaubatz, S., Lees, J. A., Lindeman, G. J. & Livingston, D. M. E2F4 is exported from the nucleus in a CRM1-dependent manner. Mol. Cell. Biol. 21, 1384–1392 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• Iavarone, A. & Massague, J. E2F and histone deacetylase mediate transforming growth factor-β repression of cdc25A during keratinocyte cell cycle arrest. Mol. Cell. Biol. 19, 916–922 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Dalton, S. Cell cycle regulation of the human CDC2 gene. EMBO J. 11, 1797–1804 (1992).
  Article CAS PubMed PubMed Central Google Scholar
• Lam, E. W. & Watson, R. J. An E2F-binding site mediates cell-cycle regulated repression of mouse B-myb transcription. EMBO J. 12, 2705–2713 (1993).
  Article CAS PubMed PubMed Central Google Scholar
• 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. 8, 1526–1537 (1994).
  Article CAS PubMed Google Scholar
• 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. 15, 6901–6913 (1995).
  Article CAS PubMed PubMed Central Google Scholar
• Huet, X., Rech, J., Plet, A., Vie, A. & Blanchard, J. M. Cyclin A expression is under negative transcriptional control during the cell cycle. Mol. Cell. Biol. 16, 3789–3798 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Zwicker, J., Liu, N., Engeland, K., Lucibello, F. C. & Muller, R. Cell cycle regulation of E2F site occupation in vivo. Science 271, 1595–1597 (1996).
  Article CAS PubMed Google Scholar
• Bruce, J. L., Hurford, R. K. Jr, Classon, M., Koh, J. & Dyson, N. Requirements for cell cycle arrest by p16INK4a. Mol. Cell 6, 737–742 (2000).
  Article CAS PubMed Google Scholar
• Gaubatz, S. et al. E2F4 and E2F5 play an essential role in pocket protein-mediated G1 control. Mol. Cell 6, 729–735 (2000).This study shows that E2f4–E2f5 double mutant MEFs are unable to arrest in response to the over-expression of the Cdk inhibitor p16, providing direct genetic evidence for the role of the repressive E2Fs in mediating cell-cycle exit.
  Article CAS PubMed Google Scholar
• 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. 11, 1447–1463 (1997).The combined loss of p107 and p130 is shown to cause a significant upregulation in the expression of known E2F-responsive genes in G0/G1 cells, and supports the role of these pocket proteins in the repression of these target genes.
  Article CAS PubMed Google Scholar
• Lindeman, G. J. et al. A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting. Genes Dev. 12, 1092–1098 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Rempel, R. E. et al. Loss of E2F4 activity leads to abnormal development of multiple cellular lineages. Mol. Cell 6, 293–306 (2000).
  Article CAS PubMed Google Scholar
• Persengiev, S. P., Kondova, I. I. & Kilpatrick, D. L. E2F4 actively promotes the initiation and maintenance of nerve growth factor-induced cell differentiation. Mol. Cell. Biol. 19, 6048–6056 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• Cobrinik, D. et al. Shared role of the pRB-related p130 and p107 proteins in limb development. Genes Dev. 10, 1633–1644 (1996).
  Article CAS PubMed Google Scholar
• Dahiya, A., Wong, S., Gonzalo, S., Gavin, M. & Dean, D. C. Linking the Rb and polycomb pathways. Mol. Cell 8, 557–569 (2001).This paper is one of an important series from the Dean lab that examines the ability of pRB to associate with histone-modifying enzymes and repress E2F-responsive genes. Its primary focus is to show that an E2F–pRB–CtBP–HPC2 complex can repress the cyclin A gene. However, it also provides key information about in vivo timing of the pRB-mediated transcriptional repression. Using ChIP assays, the authors confirm the finding that pRB does not associate with E2F-responsive promoters in cells that retain the ability to divide. They further show that pRB becomes promoter bound in cells that have to be induced to exit the cell cycle permanently through the sustained expression of p16.
  Article CAS PubMed Google Scholar
• Altiok, S., Xu, M. & Spiegelman, B. M. PPAR-γ induces cell cycle withdrawal: inhibition of E2F/DP DNA-binding activity via down-regulation of PP2A. Genes Dev. 11, 1987–1998 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Slomiany, B. A., D'Arigo, K. L., Kelly, M. M. & Kurtz, D. T. C/EBPα inhibits cell growth via direct repression of E2F-DP-mediated transcription. Mol. Cell. Biol. 20, 5986–5997 (2000).
  Article CAS PubMed PubMed Central Google Scholar
• Porse, B. T. et al. E2F repression by C/EBPα is required for adipogenesis and granulopoiesis in vivo. Cell 107, 247–258 (2001).
  Article CAS PubMed Google Scholar
• Chen, P. L., Riley, D. J., Chen, Y. & Lee, W. H. Retinoblastoma protein positively regulates terminal adipocyte differentiation through direct interaction with C/EBPs. Genes Dev. 10, 2794–2804 (1996).
  Article CAS PubMed Google Scholar
• Chen, P. L., Riley, D. J., Chen-Kiang, S. & Lee, W. H. Retinoblastoma protein directly interacts with and activates the transcription factor NF-IL6. Proc. Natl Acad. Sci. USA 93, 465–469 (1996).
  Article CAS PubMed PubMed Central Google Scholar
• Thomas, D. M. et al. The retinoblastoma protein acts as a transcriptional coactivator required for osteogenic differentiation. Mol. Cell 8, 303–316 (2001).
  Article CAS PubMed Google Scholar
• Morkel, M., Wenkel, J., Bannister, A. J., Kouzarides, T. & Hagemeier, C. An E2F-like repressor of transcription. Nature 390, 567–568 (1997).
  Article CAS PubMed Google Scholar
• Cartwright, P., Muller, H., Wagener, C., Holm, K. & Helin, K. E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription. Oncogene 17, 611–623 (1998).
  Article CAS PubMed Google Scholar
• Gaubatz, S., Wood, J. G. & Livingston, D. M. Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6. Proc. Natl Acad. Sci. USA 95, 9190–9195 (1998).
  Article CAS PubMed PubMed Central Google Scholar
• Trimarchi, J. M., Fairchild, B., Wen, J. & Lees, J. A. The E2F6 transcription factor is a component of the mammalian Bmi1-containing polycomb complex. Proc. Natl Acad. Sci. USA 98, 1519–1524 (2001).
  Article CAS PubMed PubMed Central Google Scholar
• van Lohuizen, M. Functional analysis of mouse Polycomb group genes. Cell Mol. Life Sci. 54, 71–79 (1998).
  Article CAS PubMed Google Scholar
• Jacobs, J. J. & van Lohuizen, M. Cellular memory of transcriptional states by Polycomb-group proteins. Semin. Cell Dev. Biol. 10, 227–235 (1999).
  Article CAS PubMed Google Scholar
• Francis, N. J. & Kingston, R. E. Mechanisms of transcriptional memory. Nature Rev. Mol. Cell Biol. 2, 409–421 (2001).
  Article CAS Google Scholar
• Haupt, Y., Alexander, W. S., Barri, G., Klinken, S. P. & Adams, J. M. Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in μ-myc transgenic mice. Cell 65, 753–763 (1991).
  Article CAS PubMed Google Scholar
• van Lohuizen, M. et al. Identification of cooperating oncogenes in μ-myc transgenic mice by provirus tagging. Cell 65, 737–752 (1991).
  Article CAS PubMed Google Scholar
• Jacobs, J. J. et al. Bmi-1 collaborates with c-Myc in tumorigenesis by inhibiting c-Myc-induced apoptosis via INK4a/ARF. Genes Dev. 13, 2678–2690 (1999).
  Article CAS PubMed PubMed Central Google Scholar
• 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. USA 91, 6359–6363 (1994).
  Article CAS PubMed PubMed Central Google Scholar
• Frolov, M. V. et al. Functional antagonism between E2F family members. Genes Dev. 15, 2146–2160 (2001).Drosophila has two E2Fs, dE2F1 and dE2F2. This paper shows that dE2F2 is a repressor of E2F-responsive genes and its mutation almost completely suppresses the phenotypic defects that result from dE2F1-loss. So, dE2F1 and dE2F2 antogonize each others function in vivo.
  Article CAS PubMed PubMed Central Google Scholar
• Dyson, N. & Harlow, E. Adenovirus E1A targets key regulators of cell proliferation. Cancer Surv. 12, 161–195 (1992).
  CAS PubMed Google Scholar
• Lee, M. H. et al. Targeted disruption of p107: functional overlap between p107 and Rb. Genes Dev. 10, 1621–1632 (1996).
  Article CAS PubMed Google Scholar
• Aalfs, J. D. & Kingston, R. E. What does 'chromatin remodeling' mean? Trends Biochem Sci. 25, 548–555 (2000).
  Article CAS PubMed Google Scholar
• Jenuwein, T. & Allis, C. D. Translating the histone code. Science 293, 1074–1080 (2001).
  Article CAS PubMed Google Scholar