The role and regulation of friend of GATA-1 (FOG-1) during blood development in the zebrafish
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- Julio D. Amigo
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- Gabriele E. Ackermann
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- John J. Cope
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- Ming Yu
- Division of Hematology-Oncology, Children's Hospital Boston; and
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- Jeffrey D. Cooney
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- Dongdong Ma
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- Nathaniel B. Langer
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- Ebrahim Shafizadeh
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- George C. Shaw
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- Wyatt Horsely
- Division of Hematology-Oncology, Children's Hospital Boston; and
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- Nikolaus S. Trede
- Harvard Medical School, Boston;
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- Alan J. Davidson
- Harvard Medical School, Boston;
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- Bruce A. Barut
- Division of Hematology-Oncology, Children's Hospital Boston; and
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- Yi Zhou
- Harvard Medical School, Boston;
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- Sarah A. Wojiski
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- David Traver
- Division of Hematology-Oncology, Children's Hospital Boston; and
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- Tyler B. Moran
- Division of Hematology-Oncology, Children's Hospital Boston; and
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- George Kourkoulis
- Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA
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- Karl Hsu
- Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA
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- John P. Kanki
- Harvard Medical School, Boston;
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- Dhvanit I. Shah
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- Hui Feng Lin
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- Robert I. Handin
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
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- Alan B. Cantor
- Harvard Medical School, Boston;
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- Barry H. Paw
- Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston;
説明
<jats:title>Abstract</jats:title><jats:p>The nuclear protein FOG-1 binds transcription factor GATA-1 to facilitate erythroid and megakaryocytic maturation. However, little is known about the function of FOG-1 during myeloid and lymphoid development or how FOG-1 expression is regulated in any tissue. We used in situ hybridization, gain- and loss-of-function studies in zebrafish to address these problems. Zebrafish FOG-1 is expressed in early hematopoietic cells, as well as heart, viscera, and paraspinal neurons, suggesting that it has multifaceted functions in organogenesis. We found that FOG-1 is dispensable for endoderm specification but is required for endoderm patterning affecting the expression of late-stage T-cell markers, independent of GATA-1. The suppression of FOG-1, in the presence of normal GATA-1 levels, induces severe anemia and thrombocytopenia and expands myeloid-progenitor cells, indicating that FOG-1 is required during erythroid/myeloid commitment. To functionally interrogate whether GATA-1 regulates FOG-1 in vivo, we used bioinformatics combined with transgenic assays. Thus, we identified 2 cis-regulatory elements that control the tissue-specific gene expression of FOG-1. One of these enhancers contains functional GATA-binding sites, indicating the potential for a regulatory loop in which GATA factors control the expression of their partner protein FOG-1.</jats:p>
収録刊行物
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- Blood
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Blood 114 (21), 4654-4663, 2009-11-19
American Society of Hematology