Requirement of an E1A-sensitive coactivator for long-range transactivation by the β-globin locus control region

E. Camilla Forsberg, Kirby Johnson, Tatiana N. Zaboikina, Eric A. Mosser, Emery H. Bresnick*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Four erythroid-specific DNase I-hypersensitive sites at the 5'-end of the β-globin locus confer high-level transcription to the β-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 Aγ-and β-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 γ-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.

Original languageEnglish (US)
Pages (from-to)26850-26859
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number38
DOIs
StatePublished - Sep 17 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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