Requirement of an E1A-sensitive coactivator for long-range transactivation by the beta-globin locus control region
| Autor: | Tatiana N. Zaboikina, E. Camilla Forsberg, Emery H. Bresnick, Eric A. Mosser, Kirby D. Johnson |
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| Rok vydání: | 1999 |
| Předmět: |
Transcriptional Activation
Saccharomyces cerevisiae Proteins NF-E2 Transcription Factor viruses Biology Biochemistry Polymerase Chain Reaction Transactivation Mice Transcription (biology) Acetyltransferases Coactivator Tumor Cells Cultured Animals Humans Globin Molecular Biology Locus control region Histone Acetyltransferases Retinoblastoma protein Nuclear Proteins Promoter Cell Biology Locus Control Region Molecular biology Globins DNA-Binding Proteins NF-E2 Transcription Factor p45 Subunit biology.protein Trans-Activators Erythroid-Specific DNA-Binding Factors Adenovirus E1A Proteins Leukemia Erythroblastic Acute E1A-Associated p300 Protein Transcription Factors |
| Zdroj: | The Journal of biological chemistry. 274(38) |
| ISSN: | 0021-9258 |
| Popis: | Four erythroid-specific DNase I-hypersensitive sites at the 5'-end of the beta-globin locus confer high-level transcription to the beta-globin genes. To identify coactivators that mediate long-range transactivation by this locus control region (LCR), we assessed the influence of E1A, an inhibitor of the CBP/p300 histone acetylase, on LCR function. E1A strongly inhibited transactivation of Agamma- and beta-globin promoters by the HS2, HS2-HS3, and HS1-HS4 subregions of the LCR in human K562 and mouse erythroleukemia cells. Short- and long-range transactivation mediated by the LCR were equally sensitive to E1A. The E1A sensitivity was apparent in transient and stable transfection assays, and E1A inhibited expression of the endogenous gamma-globin genes. Only sites for NF-E2 within HS2 were required for E1A sensitivity in K562 cells, and E1A abolished transactivation mediated by the activation domain of NF-E2. E1A mutants defective in CBP/p300 binding only weakly inhibited HS2-mediated transactivation, whereas a mutant defective in retinoblastoma protein binding strongly inhibited transactivation. Expression of CBP/p300 potentiated HS2-mediated transactivation. Moreover, expression of GAL4-CBP strongly increased transactivation of a reporter containing HS2 with a GAL4 site substituted for the NF-E2 sites. Thus, we propose that a CBP/p300-containing coactivator complex is the E1A-sensitive factor important for LCR function. |
| Databáze: | OpenAIRE |
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