Cyclin A expression is under negative transcriptional control during the cell cycle

Huet, X.; Rech, J.; Plet, A.; Vie, A.; Blanchard, J. M.

Mol Cell Biol

1996-07 / vol 16 / pages 3789-98


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.

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Humans; Animals; Mice; *Transcription, Genetic; Molecular Sequence Data; Gene Expression Regulation; Promoter Regions (Genetics); Base Sequence; DNA Primers; Mutagenesis, Site-Directed; Sequence Homology, Nucleic Acid; Base Composition; Cell Division; *Cell Cycle; 3T3 Cells; Conserved Sequence; DNA Footprinting; Skin/cytology; Recombinant Fusion Proteins/biosynthesis; Cyclins/*biosynthesis/genetics; DNA Probes; Fibroblasts/cytology/drug effects/metabolism; Genomic Library; Luciferases/biosynthesis

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