Identification of ZBP-89 as a novel GATA-1-associated transcription factor involved in megakaryocytic and erythroid development.
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.
Woo
Andrew J
AJ
Department of Pediatric Oncology, Children's Hospital Boston/Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Moran
Tyler B
TB
Schindler
Yocheved L
YL
Choe
Seong-Kyu
SK
Langer
Nathaniel B
NB
Sullivan
Matthew R
MR
Fujiwara
Yuko
Y
Paw
Barry H
BH
Cantor
Alan B
AB
D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D041905:Erythroid Cells / Q000166:cytology / Q000378:metabolism*; D050982:GATA1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011003:Ploidies; D011485:Protein Binding; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050982:GATA1 Transcription Factor; C494689:Gata1 protein, mouse; D014157:Transcription Factors; D029961:Zebrafish Proteins; C491741:Zfp148 protein, mouse; C491740:Zfp148 protein, rat; C528125:znf148 protein, zebrafish