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Molecular and Cellular Biology, April 2008, p. 2675-2689, Vol. 28, No. 8
0270-7306/08/$08.00+0     doi:10.1128/MCB.01945-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Identification of ZBP-89 as a Novel GATA-1-Associated Transcription Factor Involved in Megakaryocytic and Erythroid Development ^,

Andrew J. Woo,¹ Tyler B. Moran,¹ Yocheved L. Schindler,¹ Seong-Kyu Choe,² Nathaniel B. Langer,² Matthew R. Sullivan,¹ Yuko Fujiwara,¹ Barry H. Paw,² and Alan B. Cantor^1*

Department of Pediatric Oncology, Children's Hospital Boston/Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115,¹ Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115²

Received 29 October 2007/ Returned for modification 16 December 2007/ Accepted 24 January 2008

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.

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* Corresponding author. Mailing address: 300 Longwood Ave., Karp 7, Children's Hospital Boston, Boston, MA 02115. Phone: (617) 919-2026. Fax: (617) 730-0222. E-mail: alan.cantor{at}childrens.harvard.edu

Published ahead of print on 4 February 2008.

Supplemental material for this article may be found at http://mcb.asm.org/.

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Molecular and Cellular Biology, April 2008, p. 2675-2689, Vol. 28, No. 8
0270-7306/08/$08.00+0     doi:10.1128/MCB.01945-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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