Cyclin A repression in quiescent cells is associated with chromatin remodeling of its promoter and requires Brahma/SNF2alpha

Coisy, M.; Roure, V.; Ribot, M.; Philips, A.; Muchardt, C.; Blanchard, J. M.; Dantonel, J. C.

Mol Cell

2004-07-02 / vol 15 / pages 43-56


Cell cycle-dependent expression of cyclin A is controlled by transcriptional repression in early phase of the cell cycle. In this study, we directly examine the chromatin structure of the mouse cyclin A promoter through in vivo micrococcal nuclease footprinting. We describe here that cyclin A repression is associated with two positioned nucleosomes and that histones progressively lose DNA contact synchronously with gene activation. This particular nucleosomal organization is disrupted by mutations of the cyclin A bipartite repressor sequence. Moreover, the same sequence recruits the chromatin remodeling factor Brahma/SNF2alpha (Brm) onto the cyclin A promoter. Accordingly, cyclin A proximal promoter is not wrapped around nucleosomes and not repressed in quiescent cells lacking Brm. These results provide molecular explanations for the transcriptional repression state of cyclin A, as well as insights into the action of Brm chromatin remodeling factor as cell cycle regulator.

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Animals; Mice; Histones/genetics/metabolism; *Nuclear Proteins; Trans-Activators/genetics/*metabolism; Mutation/genetics; DNA-Binding Proteins/genetics/*metabolism; Transcription Factors/genetics/*metabolism; Repressor Proteins/genetics; Cyclin A/*genetics; Cell Cycle/*genetics; DNA/genetics/metabolism; Cell Cycle Proteins/genetics/*metabolism; Chromatin Assembly and Disassembly/*genetics; DNA Helicases; Drosophila Proteins; Nucleosomes/genetics/metabolism; Promoter Regions (Genetics)/*genetics; Silencer Elements, Transcriptional/genetics; Swiss 3T3 Cells

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