Identification of ZBP-89 as a novel GATA-1-associated transcription factor involved in megakaryocytic and erythroid development

Mol Cell Biol. 2008 Apr;28(8):2675-89. doi: 10.1128/MCB.01945-07. Epub 2008 Feb 4.


A complete understanding of the transcriptional regulation of developmental lineages requires that all relevant factors be identified. Here, we have taken a proteomic approach to identify novel proteins associated with GATA-1, a lineage-restricted zinc finger transcription factor required for terminal erythroid and megakaryocytic maturation. We identify the Krüppel-type zinc finger transcription factor ZBP-89 as being a component of multiprotein complexes involving GATA-1 and its essential cofactor Friend of GATA-1 (FOG-1). Using chromatin immunoprecipitation assays, we show that GATA-1 and ZBP-89 cooccupy cis-regulatory elements of certain erythroid and megakaryocyte-specific genes, including an enhancer of the GATA-1 gene itself. Loss-of-function studies in zebrafish and mice demonstrate an in vivo requirement for ZBP-89 in megakaryopoiesis and definitive erythropoiesis but not primitive erythropoiesis, phenocopying aspects of FOG-1- and GATA-1-deficient animals. These findings identify ZBP-89 as being a novel transcription factor involved in erythroid and megakaryocytic development and suggest that it serves a cooperative function with GATA-1 and/or FOG-1 in a developmental stage-specific manner.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation*
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / metabolism
  • Erythroid Cells / cytology
  • Erythroid Cells / metabolism*
  • GATA1 Transcription Factor / chemistry
  • GATA1 Transcription Factor / genetics
  • GATA1 Transcription Factor / isolation & purification
  • GATA1 Transcription Factor / metabolism*
  • Megakaryocytes / cytology
  • Megakaryocytes / metabolism*
  • Mice
  • Molecular Sequence Data
  • Ploidies
  • Protein Binding
  • Rats
  • Transcription Factors / genetics
  • Transcription Factors / isolation & purification
  • Transcription Factors / metabolism*
  • Zebrafish
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / metabolism*


  • DNA-Binding Proteins
  • GATA1 Transcription Factor
  • Gata1 protein, mouse
  • Transcription Factors
  • Zebrafish Proteins
  • Zfp148 protein, mouse
  • Zfp148 protein, rat
  • znf148 protein, zebrafish