CREB-binding protein cooperates with transcription factor GATA-1 and is required for erythroid differentiation.
The transcription factor GATA-1 coordinates multiple events during terminal erythroid cell maturation. GATA-1 participates in the transcription of virtually all erythroid-specific genes, blocks apoptosis of precursor cells, and controls the balance between proliferation and cell cycle arrest. Prior studies suggest that the function of GATA-1 is mediated in part through association with transcriptional cofactors. CREB-binding protein (CBP) and its close relative p300 serve as coactivators for a variety of transcription factors involved in growth control and differentiation. We report here that CBP markedly stimulates GATA-1's transcriptional activity in transient transfection experiments in nonhematopoietic cells. GATA-1 and CBP also coimmunoprecipitate from nuclear extracts of erythroid cells. Interaction mapping pinpoints contact sites to the zinc finger region of GATA-1 and to the E1A-binding region of CBP. Expression of a conditional form of adenovirus E1A in murine erythroleukemia cells blocks differentiation and expression of endogenous GATA-1 target genes, whereas mutant forms of E1A unable to bind CBP/p300 have no effect. Our findings add GATA-1, and very likely other members of the GATA family, to the growing list of molecules implicated in the complex regulatory network surrounding CBP/p300.
Blobel
G A
GA
Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Nakajima
T
T
Eckner
R
R
Montminy
M
M
Orkin
S H
SH
D016475:3T3 Cells; D000818:Animals; D050882:CREB-Binding Protein; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology*; D050981:Erythroid-Specific DNA-Binding Factors; D004958:Estradiol / Q000494:pharmacology; D050982:GATA1 Transcription Factor; D005786:Gene Expression Regulation; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000302:isolation & purification / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015534:Trans-Activators; D014157:Transcription Factors / Q000302:isolation & purification / Q000378:metabolism*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D004958:Estradiol; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse