Amigo, J.D., Ackermann, G.E., Cope, J.J., Yu, M., Cooney, J.D., Ma, D., Langer, N.B., Shafizadeh, E., Shaw, G.C., Horsley, W., Trede, N.S., Davidson, A.J., Barut, B.A., Zhou, Y., Wojiski, S.A., Traver, D., Moran, T.B., Kourkoulis, G., Hsu, K., Kanki, J.P., Shah, D.I., Lin, H.F., Handin, R.I., Cantor, A.B., and Paw, B.H. (2009) The role and regulation of friend of GATA-1 (FOG-1) during blood development in the zebrafish. Blood. 114(21):4654-4663.
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 para-spinal neurons, suggesting that it has multifaceted functions in organogenesis. We found that FOG-1 is dispensable for endodermal 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, 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 two 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 regulatory loop in which GATA factors control the expression of their partner protein FOG-1.