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PMID: 18250154 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Molecular and cellular biology ·Vol. 28 ·No. 8 ·2008-04-00 ·Pages 2675-89

Woo AJ, Moran TB, Schindler YL, Choe SK, Langer NB, Sullivan MR, Fujiwara Y, Paw BH, Cantor AB

Abstract

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.

MeSH Terms
Amino Acid Sequence Animals Animals, Genetically Modified Cell Differentiation Cell Line DNA-Binding Proteins/genetics,isolation & purification,metabolism Embryo, Nonmammalian/cytology,embryology,metabolism Embryonic Stem Cells/cytology,metabolism Erythroid Cells/cytology,metabolism GATA1 Transcription Factor/chemistry,genetics,isolation & purification,metabolism Megakaryocytes/cytology,metabolism Mice Molecular Sequence Data Ploidies Protein Binding Rats Transcription Factors/genetics,isolation & purification,metabolism Zebrafish Zebrafish Proteins/genetics,metabolism
Chemicals
DNA-Binding Proteins GATA1 Transcription Factor Gata1 protein, mouse Transcription Factors Zebrafish Proteins Zfp148 protein, mouse Zfp148 protein, rat znf148 protein, zebrafish
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Woo Andrew J
Department of Pediatric Oncology, Children's Hospital Boston/Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Moran Tyler B
Schindler Yocheved L
Choe Seong-Kyu
Langer Nathaniel B
Sullivan Matthew R
Fujiwara Yuko
Paw Barry H
Cantor Alan B
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
Published
2008-04-00
Epub
2008-00-04
Pages
2675-89
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2293107
Subset
IM
Grants
NHLBI NIH HHS · P01 HL032262 · United States
NIDDK NIH HHS · R01 DK070838 · United States
NHLBI NIH HHS · R01 HL075705 · United States
NHLBI NIH HHS · R01 HL 075705 · United States
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