Cyclin A expression is under negative transcriptional control during the cell cycle.
Transcription of the gene coding for cyclin A, a protein required for S-phase transit, is cell cycle regulated and is restricted to proliferating cells. To further explore transcriptional regulation linked to cell division cycle control, a genomic clone containing 5' flanking sequences of the murine cyclin A gene was isolated. When it was fused to a luciferase reporter gene, it was shown to function as a proliferation-regulated promoter in NIH 3T3 cells. Transcription of the mouse cyclin A gene is negatively regulated by arrest of cell proliferation. A mutation of a GC-rich sequence conserved between mice and humans is sufficient to relieve transcriptional repression, resulting in a promoter with constitutively high activity. In agreement with this result, in vivo footprinting reveals a protection of the cell cycle-responsive element in G0/early G1 cells which is not observed at later stages of the cell cycle. Moreover, the footprint is present in dimethyl sulfoxide-induced differentiating and not in proliferating Friend erythroleukemia cells. Conversely, two other sites, which in vitro bind ATF-1 and NF-Y, respectively, are constitutively occupied throughout cell cycle progression.
Huet
X
X
Institut de Génétique Moléculaire de Montpellier, CNRS UMR 5535, France.
Rech
J
J
Plet
A
A
Vié
A
A
Blanchard
J M
JM
D016475:3T3 Cells; D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D002453:Cell Cycle; D002455:Cell Division; D017124:Conserved Sequence; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D018983:DNA Footprinting; D017931:DNA Primers; D015342:DNA Probes; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D015698:Genomic Library; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012689:Sequence Homology, Nucleic Acid; D012867:Skin / Q000166:cytology; D014158:Transcription, Genetic
D016213:Cyclins; D017931:DNA Primers; D015342:DNA Probes; D011993:Recombinant Fusion Proteins; D008156:Luciferases