Cell Cycle Regulation of E2F Site Occupation in Vivo

DNA-binding E2F complexes have been identified throughout the mammalian cell cycle, including the transcriptionally inactive complexes with pocket proteins, which occur early in the prereplicative G1 phase of the cycle, and the transactivating free E2F, which increases in late G1. Here, a regulatory B-myb promoter site was shown to bind with high affinity to free E2F and to E2F-pocket protein complexes in an indistinguishable way in vitro. In contrast, in vivo footprinting with NIH 3T3 cells demonstrated E2F site occupation specifically in early G1, when the B-myb promoter is inactive. These observations indicate that a novel mechanism governs E2F-DNA interactions during the cell cycle and emphasize the relevance of E2F site-directed transcriptional repression.

[1]  C. Wittenberg,et al.  Rapid Degradation of the G1 Cyclin Cln2 Induced by CDK-Dependent Phosphorylation , 1996, Science.

[2]  N. Andrews,et al.  Multiple Proteins Interact with the Nuclear Inhibitory Protein Repressor Element in the Human Interleukin-3 Promoter (*) , 1995, The Journal of Biological Chemistry.

[3]  F. C. Lucibello,et al.  Cell cycle regulation of cdc25C transcription is mediated by the periodic repression of the glutamine-rich activators NF-Y and Sp1. , 1995, Nucleic acids research.

[4]  F. C. Lucibello,et al.  Cell cycle regulation of the cyclin A, cdc25C and cdc2 genes is based on a common mechanism of transcriptional repression. , 1995, The EMBO journal.

[5]  S. Weintraub,et al.  Mechanism of active transcriptional repression by the retinoblastoma protein , 1995, Nature.

[6]  R. Müller,et al.  Transcriptional regulation during the mammalian cell cycle. , 1995, Trends in genetics : TIG.

[7]  F. C. Lucibello,et al.  Periodic cdc25C transcription is mediated by a novel cell cycle‐regulated repressor element (CDE). , 1995, The EMBO journal.

[8]  J. Lawrence,et al.  E2F-4, a new member of the E2F transcription factor family, interacts with p107. , 1994, Genes & development.

[9]  L. Zhu,et al.  E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. , 1994, Genes & development.

[10]  B. Dynlacht,et al.  Differential regulation of E2F transactivation by cyclin/cdk2 complexes. , 1994, Genes & development.

[11]  Wilhelm Krek,et al.  Negative regulation of the growth-promoting transcription factor E2F-1 by a stably bound cyclin A-dependent protein kinase , 1994, Cell.

[12]  N. L. Thangue,et al.  DP and E2F proteins: components of a heterodimeric transcription factor implicated in cell cycle control , 1994 .

[13]  T. Crook,et al.  HPV16 E7 oncoprotein deregulates B‐myb expression: correlation with targeting of p107/E2F complexes. , 1994, The EMBO journal.

[14]  E. Lam,et al.  An E2F‐binding site mediates cell‐cycle regulated repression of mouse B‐myb transcription. , 1993, The EMBO journal.

[15]  K. Helin,et al.  The retinoblastoma protein as a transcriptional repressor. , 1993, Trends in cell biology.

[16]  J. Nevins,et al.  E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. , 1992, Science.

[17]  Peggy J. Farnham,et al.  Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties , 1992, Cell.

[18]  Marc Vidal,et al.  A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F , 1992, Cell.

[19]  H. Stunnenberg,et al.  Identification of multiple SRF N‐terminal phosphorylation sites affecting DNA binding properties. , 1992, The EMBO journal.

[20]  M. Ewen,et al.  Molecular cloning, chromosomal mapping, and expression of the cDNA for p107, a retinoblastoma gene product-related protein , 1991, Cell.

[21]  T. Hunt,et al.  Cyclin A and the retinoblastoma gene product complex with a common transcription factor , 1991, Nature.

[22]  W. Kaelin,et al.  The T/E1A-binding domain of the retinoblastoma product can interact selectively with a sequence-specific DNA-binding protein , 1991, Cell.

[23]  Joseph R. Nevins,et al.  The E2F transcription factor is a cellular target for the RB protein , 1991, Cell.

[24]  J. Nevins,et al.  A role for the adenovirus inducible E2F transcription factor in a proliferation dependent signal transduction pathway. , 1990, The EMBO journal.

[25]  B. Wold,et al.  Genomic sequencing and methylation analysis by ligation mediated PCR. , 1989, Science.

[26]  S. Friend,et al.  Structure and expression of the murine retinoblastoma gene and characterization of its encoded protein. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[27]  G. Superti-Furga,et al.  Mutually exclusive interaction of the CCAAT-binding factor and of a displacement protein with overlapping sequences of a histone gene promoter , 1987, Cell.