The role and regulation of friend of GATA-1 (FOG-1) during blood development in the zebrafish

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...

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Published in:	Blood Vol. 114; no. 21; pp. 4654 - 4663
Main Authors:	Amigo, Julio D., Ackermann, Gabriele E., Cope, John J., Yu, Ming, Cooney, Jeffrey D., Ma, Dongdong, Langer, Nathaniel B., Shafizadeh, Ebrahim, Shaw, George C., Horsely, Wyatt, Trede, Nikolaus S., Davidson, Alan J., Barut, Bruce A., Zhou, Yi, Wojiski, Sarah A., Traver, David, Moran, Tyler B., Kourkoulis, George, Hsu, Karl, Kanki, John P., Shah, Dhvanit I., Lin, Hui Feng, Handin, Robert I., Cantor, Alan B., Paw, Barry H.
Format:	Journal Article
Language:	English
Published:	Washington, DC Elsevier Inc 19-11-2009 Americain Society of Hematology American Society of Hematology
Series:	Hematopoiesis and Stem Cells
Subjects:	Animals Biological and medical sciences Embryonic Development - physiology GATA1 Transcription Factor - genetics GATA1 Transcription Factor - metabolism Gene Expression Regulation, Developmental Hematologic and hematopoietic diseases Hematopoiesis - physiology Hematopoiesis and Stem Cells In Situ Hybridization Medical sciences Nuclear Proteins - genetics Nuclear Proteins - metabolism Oligonucleotide Array Sequence Analysis Polymerase Chain Reaction Regulatory Elements, Transcriptional - genetics Zebrafish - embryology Zebrafish Proteins - genetics Zebrafish Proteins - metabolism Signal transduction Vertebrata Brachydanio rerio Hematology Pisces Transcription factor GATA1 Blood
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 J.D.A., G.E.A., and J.J.C. contributed equally to this study.
ISSN:	0006-4971 1528-0020
DOI:	10.1182/blood-2008-12-189910