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| Content Provider | PubMed Central |
|---|---|
| Author | Sinha, Anupama Faller, Douglas V. Denis, Gerald V. |
| Copyright Year | 2005 |
| Abstract | Cyclin A is regulated primarily through transcription control during the mammalian cell cycle. A dual mechanism of cyclin A transcriptional repression involves, on the one hand, promoter-bound inhibitory complexes of E2F transcription factors and RB (retinoblastoma) family proteins, and on the other, chromatin-directed histone deacetylase activity that is recruited to the cyclin A promoter early in the cell cycle in association with these RB proteins. This dual regulation maintains transcriptional silence of the cyclin A locus until its transcription is required in S-phase. At that time, RB family members dissociate from E2F proteins and nucleosomal restructuring of the locus takes place, to permit transcriptional activation and resultant S-phase progression to proceed. We have identified a double bromo-domain-containing protein Brd2, which exhibits apparent ‘scaffold’ or transcriptional adapter functions and mediates recruitment of both E2F transcription factors and chromatin-remodelling activity to the cyclin A promoter. We have shown previously that Brd2-containing nuclear, multiprotein complexes contain E2F-1 and -2. In the present study, we show that, in S-phase, they also contain histone H4-directed acetylase activity. Overexpression of Brd2 in fibroblasts accelerates the cell cycle through increased expression of cyclin A and its associated cyclin-dependent kinase activity. Chromatin immunoprecipitation studies show that Brd2 is physically present at the cyclin A promoter and its overexpression promotes increased histone H4 acetylation at the promoter as it becomes transcriptionally active, suggesting a new model for the dual regulation of cyclin A. |
| Related Links | http://dx.doi.org/10.1042/bj20041793 |
| Ending Page | 269 |
| Page Count | 13 |
| Starting Page | 257 |
| File Format | |
| ISSN | 02646021 |
| e-ISSN | 14708728 |
| Journal | Biochemical Journal |
| Issue Number | Pt 1 |
| Volume Number | 387 |
| Language | English |
| Publisher | Portland Press Ltd. |
| Publisher Date | 2005-04-01 |
| Access Restriction | Open |
| Rights Holder | Portland Press Ltd. |
| Subject Keyword | Cell Biology Biochemistry Molecular Biology Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Biology Biochemistry |
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