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

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.
Blood   114(21): 4654-4663 (Journal)
Registered Authors
Ackermann, Gabriele, Amigo, Julio, Barut, Bruce, Cope, John, Davidson, Alan, Handin, Robert, Hsu, Karl, Kanki, John, Kourkoulis, George D., Lin, Hui-feng, Ma, Dongdong, Paw, Barry, Shafizadeh, Ebrahim, Shah, Dhvanit I., Shaw, George C., Traver, David, Trede, Nick, Zhou, Yi
MeSH Terms
  • Animals
  • Embryonic Development/physiology*
  • GATA1 Transcription Factor/genetics
  • GATA1 Transcription Factor/metabolism
  • Gene Expression Regulation, Developmental*
  • Hematopoiesis/physiology
  • In Situ Hybridization
  • 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
19729519 Full text @ Blood
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes