Cyclin A repression in quiescent cells is associated with chromatin remodeling of its promoter and requires Brahma/SNF2alpha.
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.
Coisy
Marjorie
M
Institut de Génétique Moléculaire, CNRS, UMR 5535, 1919 Route de Mende, 34293 Montpellier cedex 5, France.
Roure
Virginie
V
Ribot
Magali
M
Philips
Alexandre
A
Muchardt
Christian
C
Blanchard
Jean-Marie
JM
Dantonel
Jean-Christophe
JC
D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D019925:Cyclin A / Q000235:genetics*; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D006657:Histones / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D037941:Silencer Elements, Transcriptional / Q000235:genetics; D041701:Swiss 3T3 Cells; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D019925:Cyclin A; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D012097:Repressor Proteins; C499503:Smarca2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; C086469:brm protein, Drosophila; D004247:DNA; C513194:Smarca4 protein, mouse; D004265:DNA Helicases