A B-myb promoter corepressor site facilitates in vivo occupation of the adjacent E2F site by p107-E2F and p130-E2F complexes

被引:20
作者
Catchpole, S
Tavner, F
Le Cam, L
Sardet, C
Watson, RJ
机构
[1] Univ London Imperial Coll Sci Technol & Med, Fac Med, Ludwig Inst Canc Res, London W2 1PG, England
[2] Univ London Imperial Coll Sci Technol & Med, Fac Med, Sect Virol & Cell Biol, London W2 1PG, England
[3] Inst Genet Mol, CNRS, UMR 5535, F-34293 Montpellier, France
关键词
D O I
10.1074/jbc.M202960200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Transcription from the B-myb (MybL2 gene) promoter is strictly cell cycle-regulated by repression mediated through an E2F site during G(0)/early G(1). We report here the characterization of a corepressor site (downstream repression site (DRS)) required for this activity that is closely linked to the E2F site. Systematic mutagenesis of the DRS enabled a consensus to be derived, and it is notable that this sequence is compatible with cell cycle gene homology region sequences associated with cell cycle-dependent elements in the cyclin A, cdc2, and CDC25C promoters. The B-myb promoter is inappropriately active during Go in mouse embryo fibroblasts lacking the p107 and p130 pocket proteins, and we show that the ability of transfected p107 and p130 to re-impose repression on the promoter is dependent on the DRS. In contrast, transfected Rb was unable to repress the B-myb promoter. Consistent with the notion that Rb-E2F complexes are unable to bind the B-myb promoter E2F site in vivo, footprinting showed that this site is unoccupied in cells lacking p107 and p130. Chromatin immunoprecipitation assays showed a requirement for the DRS in recruiting p107 and p130 complexes to the B-myb promoter, indicating that in vivo the DRS governs the occupancy of the adjacent E2F site by transcriptional repressors.
引用
收藏
页码:39015 / 39024
页数:10
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