Transcription factor ZBP-89 cooperates with histone acetyltransferase p300 during butyrate activation of p21waf1 transcription in human cells.
Inducible p53-independent regulation of the cyclin-dependent kinase inhibitor p21(waf1) transcription is mediated through proximal GC-rich sites. Prior studies have shown that Sp1, Sp3, and the histone acetylase co-activator p300 are components of the complexes binding to these sites. Although Sp1 and Sp3 collaborate with p300, a direct interaction between Sp1 ... and p300 does not occur. This study sought to determine whether ZBP-89 rather than Sp1 is the direct target of p300 during butyrate induction of p21(waf1). ZBP-89 (BFCOL1, BERF-1, ZNF 148) is a Krueppel-type zinc finger transcription factor that binds to GC-rich elements and represses or activates known target genes. Adenoviral-mediated expression of ZBP-89 in HT-29 cells revealed that ZBP-89 potentiates butyrate induction of endogenous p21(waf1) gene expression. Further, cotransfection of a ZBP-89 expression vector with a 2.3-kilobase p21(waf1) reporter recapitulated the potentiation by butyrate. DNase I footprinting analysis of the human p21(waf1) promoter with recombinant ZBP-89 identified a binding site at -245 to -215. Electrophoretic mobility shift assays confirmed that both recombinant and endogenous ZBP-89 and Sp1 bind to this element. The potentiation was abolished in the presence of adenoviral protein E1A. Deletion of the N-terminal domain of ZBP-89 abolished the potentiation mediated by butyrate treatment. This same deletion mutant abolished the ZBP-89 interaction with p300. Cotransfection of p300 with ZBP-89 stimulated the p21(waf1) promoter in the absence of butyrate. p300 co-precipitated with ZBP-89 but not with Sp1, whereas ZBP-89 co-precipitated with Sp1. Together, these findings demonstrate that ZBP-89 also plays a critical role in butyrate activation of the p21(waf1) promoter and reveals preferential cooperation of this four-zinc finger transcription factor with p300.
Mesh Terms:
Acetyltransferases, Adenovirus E1A Proteins, Base Sequence, Binding Sites, Butyrates, Cell Cycle Proteins, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases, Cyclins, DNA Footprinting, DNA-Binding Proteins, Histone Acetyltransferases, Histones, Humans, Models, Genetic, Molecular Sequence Data, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, Recombinant Proteins, Repressor Proteins, Sp1 Transcription Factor, Transcription Factors, Transcriptional Activation, Zinc Fingers, p300-CBP Transcription Factors
Acetyltransferases, Adenovirus E1A Proteins, Base Sequence, Binding Sites, Butyrates, Cell Cycle Proteins, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinases, Cyclins, DNA Footprinting, DNA-Binding Proteins, Histone Acetyltransferases, Histones, Humans, Models, Genetic, Molecular Sequence Data, Promoter Regions, Genetic, Protein Binding, Protein Structure, Tertiary, Recombinant Proteins, Repressor Proteins, Sp1 Transcription Factor, Transcription Factors, Transcriptional Activation, Zinc Fingers, p300-CBP Transcription Factors
J. Biol. Chem.
Date: Sep. 29, 2000
PubMed ID: 10899165
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