title: GATA-1 and c-myb crosstalk during red blood cell differentiation through GATA-1 binding sites in the c-myb promoter.
abstract: GATA-1 and c-Myb transcription factors represent key regulators of red blood cell development. GATA-1 is upregulated and c-myb proto-oncogene expression is downregulated when red cell progenitors differentiate into erythrocytes. Here we have employed a culture system, that faithfully recapitulates red blood cell differentiation in vitro, to follow the kinetics of GATA-1 and c-myb expression. We show that c-myb proto-oncogene expression is high in progenitors and effectively downregulated at the time when nuclear GATA-1 accumulates and cells differentiate into erythrocytes. Additionally, we identified two GATA-1 binding sites within the c-myb promoter and demonstrate that GATA-1 protein binds to these sites in vitro. Furthermore, GATA-1 represses c-myb expression through one of the GATA-1 binding sites in transient transfection experiments and this requires FOG-1. Thus, our study provides evidence for a direct molecular link between GATA-1 activity and c-myb proto-oncogene expression during terminal red cell differentiation.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: Petr
authors.initials: P
authors.lastname: Bartůnek
authors.forename: Jarmila
authors.initials: J
authors.lastname: Králová
authors.forename: Gitta
authors.initials: G
authors.lastname: Blendinger
authors.forename: Michal
authors.initials: M
authors.lastname: Dvorák
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000502:physiology; D002642:Chick Embryo; D002645:Chickens; D004268:DNA-Binding Proteins / Q000502:physiology*; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors; D004920:Erythropoiesis / Q000502:physiology*; D005347:Fibroblasts; D050982:GATA1 Transcription Factor; D018507:Gene Expression Regulation, Developmental; D020570:Genes, myb; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*; D019089:Stem Cell Factor / Q000494:pharmacology; D014157:Transcription Factors / Q000502:physiology*; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; C000715470:MAS1 protein, human; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D020598:Proto-Oncogene Proteins c-myb; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D019089:Stem Cell Factor; D014157:Transcription Factors; C498432:ZFPM1 protein, human