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

Blood. 2009 Nov 19;114(21):4654-63. doi: 10.1182/blood-2008-12-189910. Epub 2009 Sep 3.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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


  • GATA1 Transcription Factor
  • Nuclear Proteins
  • Zebrafish Proteins
  • gata1a protein, zebrafish