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PMID: 15510213 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

E2Fs link the control of G1/S and G2/M transcription.

The EMBO journal ·Vol. 23 ·No. 23 ·2004-11-24 ·Pages 4615-26

Zhu W, Giangrande PH, Nevins JR

Abstract

Previous work has provided evidence for E2F-dependent transcription control of both G1/S- and G2/M-regulated genes. Analysis of the G2-regulated cdc2 and cyclin B1 genes reveals the presence of both positive- and negative-acting E2F promoter elements. Additional elements provide both positive (CCAAT and Myb) and negative (CHR) control. Chromatin immunoprecipitation assays identify multiple interactions of E2F proteins that include those previously shown to activate and repress transcription. We find that E2F1, E2F2, and E2F3 bind to the positive-acting E2F site in the cdc2 promoter, whereas E2F4 binds to the negative-acting site. We also find that binding of an activator E2F is dependent on an adjacent CCAAT site that is bound by the NF-Y transcription factor and binding of a repressor E2F is dependent on an adjacent CHR element, suggesting a role for cooperative interactions in determining both activation and repression. Finally, the kinetics of B-Myb interaction with the G2-regulated promoters coincides with the activation of the genes, and RNAi-mediated reduction of B-Myb inhibits expression of cyclin B1 and cdc2. The ability of B-Myb to interact with the cdc2 promoter is dependent on an intact E2F binding site. These results thus point to a role for E2Fs, together with B-Myb, which is an E2F-regulated gene expressed at G1/S, in linking the regulation of genes at G1/S and G2/M.

MeSH Terms
Animals CDC2 Protein Kinase/genetics,metabolism Cell Cycle/genetics,physiology Cell Cycle Proteins/genetics,metabolism Cells, Cultured Chromatin Immunoprecipitation Cyclin B/genetics,metabolism Cyclin B1 DNA-Binding Proteins/genetics,metabolism E2F Transcription Factors E2F1 Transcription Factor E2F3 Transcription Factor G1 Phase/genetics,physiology G2 Phase/genetics,physiology Gene Expression Regulation Mutation Promoter Regions, Genetic RNA, Small Interfering/metabolism Rats Transcription Factors/genetics,metabolism Transcription, Genetic
Chemicals
Ccnb1 protein, rat Cell Cycle Proteins Cyclin B Cyclin B1 DNA-Binding Proteins E2F Transcription Factors E2F1 Transcription Factor E2F3 Transcription Factor E2f1 protein, rat Mybl2 protein, rat RNA, Small Interfering Transcription Factors CDC2 Protein Kinase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zhu Wencheng
Department of Molecular Genetics and Microbiology, Duke Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, NC 27710, USA.
Giangrande Paloma H
Nevins Joseph R
References (36)
36 references, click to expand
  1. Cell cycle-dependent regulation of the cyclin B1 promoter.
    J Biol Chem. 1995 Nov 24;270(47):28419-24 PMID: 7499347
  2. p53 negatively regulates cdc2 transcription via the CCAAT-binding NF-Y transcription factor.
    J Biol Chem. 1999 Oct 15;274(42):29677-82 PMID: 10514438
  3. 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):2905-10 PMID: 8760872
  4. Cell-cycle regulation of gene expression by transcriptional repression.
    Trends Genet. 1997 Jan;13(1):3-6 PMID: 9009839
  5. E2F-mediated growth regulation requires transcription factor cooperation.
    J Biol Chem. 1997 Jul 18;272(29):18367-74 PMID: 9218478
  6. Transcriptional activation of the p34cdc2 gene by cdc2 promoter binding factor/nuclear factor-Y in fetal rat ventricular myocytes.
    Circ Res. 1998 Feb 9;82(2):251-60 PMID: 9468196
  7. Myb proteins in life, death and differentiation.
    Curr Opin Genet Dev. 1998 Feb;8(1):76-81 PMID: 9529609
  8. Role of the CCAAT-binding protein CBF/NF-Y in transcription.
    Trends Biochem Sci. 1998 May;23(5):174-8 PMID: 9612081
  9. Coordination of growth and cell division in the Drosophila wing.
    Cell. 1998 Jun 26;93(7):1183-93 PMID: 9657151
  10. A new model of cell cycle-regulated transcription: repression of the cyclin A promoter by CDF-1 and anti-repression by E2F.
    Oncogene. 1998 Jun 11;16(23):2957-63 PMID: 9662327
  11. The regulation of E2F by pRB-family proteins.
    Genes Dev. 1998 Aug 1;12(15):2245-62 PMID: 9694791
  12. Analysis of promoter binding by the E2F and pRB families in vivo: distinct E2F proteins mediate activation and repression.
    Genes Dev. 2000 Apr 1;14(7):804-16 PMID: 10766737
  13. Role for E2F in control of both DNA replication and mitotic functions as revealed from DNA microarray analysis.
    Mol Cell Biol. 2001 Jul;21(14):4684-99 PMID: 11416145
  14. E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints.
    Genes Dev. 2002 Jan 15;16(2):245-56 PMID: 11799067
  15. E2Fs up-regulate expression of genes involved in DNA replication, DNA repair and mitosis.
    Oncogene. 2002 Jan 17;21(3):437-46 PMID: 11821956
  16. Myb controls G(2)/M progression by inducing cyclin B expression in the Drosophila eye imaginal disc.
    EMBO J. 2002 Feb 15;21(4):675-84 PMID: 11847115
  17. E2F mediates cell cycle-dependent transcriptional repression in vivo by recruitment of an HDAC1/mSin3B corepressor complex.
    Genes Dev. 2002 Apr 15;16(8):933-47 PMID: 11959842
  18. Transcriptional regulatory networks in Saccharomyces cerevisiae.
    Science. 2002 Oct 25;298(5594):799-804 PMID: 12399584
  19. Interaction of YY1 with E2Fs, mediated by RYBP, provides a mechanism for specificity of E2F function.
    EMBO J. 2002 Nov 1;21(21):5775-86 PMID: 12411495
  20. Identification of E-box factor TFE3 as a functional partner for the E2F3 transcription factor.
    Mol Cell Biol. 2003 Jun;23(11):3707-20 PMID: 12748276
  21. Three CCAAT-boxes and a single cell cycle genes homology region (CHR) are the major regulating sites for transcription from the human cyclin B2 promoter.
    Gene. 2003 Jul 17;312:225-37 PMID: 12909359
  22. Distinct recruitment of E2F family members to specific E2F-binding sites mediates activation and repression of the E2F1 promoter.
    Oncogene. 2003 Oct 23;22(48):7632-41 PMID: 14576826
  23. Combinatorial gene control involving E2F and E Box family members.
    EMBO J. 2004 Mar 24;23(6):1336-47 PMID: 15014447
  24. DNA binding activity and transcriptional activator function of the human B-myb protein compared with c-MYB.
    J Biol Chem. 1990 Jun 5;265(16):9280-4 PMID: 2160970
  25. Nucleotide preferences in sequence-specific recognition of DNA by c-myb protein.
    Nucleic Acids Res. 1991 Jul 25;19(14):3913-9 PMID: 1861984
  26. Cell cycle regulation of the human cdc2 gene.
    EMBO J. 1992 May;11(5):1797-804 PMID: 1582409
  27. c-myb transactivates cdc2 expression via Myb binding sites in the 5'-flanking region of the human cdc2 gene.
    J Biol Chem. 1993 Jan 25;268(3):2255-9 PMID: 8420994
  28. 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):4514-22 PMID: 7556094
  29. 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):3822-30 PMID: 7479023
  30. 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):6901-13 PMID: 8524257
  31. Toward an understanding of the functional complexity of the E2F and retinoblastoma families.
    Cell Growth Differ. 1998 Aug;9(8):585-93 PMID: 9716176
  32. Cell cycle-dependent usage of transcriptional start sites. A novel mechanism for regulation of cyclin B1.
    J Biol Chem. 1998 Nov 20;273(47):31505-9 PMID: 9813064
  33. The cell-cycle regulated transcription factor B-Myb is phosphorylated by cyclin A/Cdk2 at sites that enhance its transactivation properties.
    Oncogene. 1998 Nov 26;17(21):2679-89 PMID: 9840932
  34. Structural basis of DNA recognition by the heterodimeric cell cycle transcription factor E2F-DP.
    Genes Dev. 1999 Mar 15;13(6):666-74 PMID: 10090723
  35. The myb gene family in cell growth, differentiation and apoptosis.
    Oncogene. 1999 May 13;18(19):3017-33 PMID: 10378697
  36. E2F-1 accumulation bypasses a G1 arrest resulting from the inhibition of G1 cyclin-dependent kinase activity.
    Genes Dev. 1995 Dec 1;9(23):2873-87 PMID: 7498785
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1038/sj.emboj.7600459
Published
2004-11-24
Epub
2004-00-28
Pages
4615-26
Language
English
Region
England
NLM ID
8208664
PMCID
PMC533046
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.emboj.7600459 PMC Full Text View journal details
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