Cell cycle regulation of the murine cyclin E gene depends on an E2F binding site in the promoter.
Cyclin E controls progression through the G1 phase of the cell cycle in mammalian fibroblasts and potentially in many other cell types. Cyclin E is a rate-limiting activator of cdk2 kinase in late G1. The abundance of cyclin E is controlled by phase-specific fluctuations in the mRNA level; in mammalian fibroblasts, mRNA is not detected under conditions of serum starvation and is accumulated upon serum stimulation, with expression starting in mid-G1. Here, we report the cloning of the murine cyclin E promoter. We isolated a 3.8-kb genomic fragment that contains several transcriptional start sites and confers cell cycle regulation on a luciferase reporter gene. This fragment also supports transcriptional activation by adenovirus E1A, a known upstream regulator of cyclin E gene expression. An E2F binding site which is required for G1-specific activation of the cyclin E promoter in synchronized NIH 3T3 cells was identified in this fragment.
Botz
J
J
Forschungsschwerpunkt Angewandte Tumorvirologie,Deutsches Krebsforschungszentrum für Molekulare Biologie der Universität, Heidelberg, Germany.
Zerfass-Thome
K
K
Spitkovsky
D
D
Delius
H
H
Vogt
B
B
Eilers
M
M
Hatzigeorgiou
A
A
Jansen-Dürr
P
P
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003001:Cloning, Molecular; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005786:Gene Expression Regulation; D006801:Humans; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009838:Oligodeoxyribonucleotides; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000096:biosynthesis; D056465:Retinoblastoma-Binding Protein 1; D012689:Sequence Homology, Nucleic Acid; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors