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 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.
Amigo
Julio D
JD
Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston, MA 02115, USA.
Ackermann
Gabriele E
GE
Cope
John J
JJ
Yu
Ming
M
Cooney
Jeffrey D
JD
Ma
Dongdong
D
Langer
Nathaniel B
NB
Shafizadeh
Ebrahim
E
Shaw
George C
GC
Horsely
Wyatt
W
Trede
Nikolaus S
NS
Davidson
Alan J
AJ
Barut
Bruce A
BA
Zhou
Yi
Y
Wojiski
Sarah A
SA
Traver
David
D
Moran
Tyler B
TB
Kourkoulis
George
G
Hsu
Karl
K
Kanki
John P
JP
Shah
Dhvanit I
DI
Lin
Hui Feng
HF
Handin
Robert I
RI
Cantor
Alan B
AB
Paw
Barry H
BH
D000818:Animals; D047108:Embryonic Development / Q000502:physiology*; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006410:Hematopoiesis / Q000502:physiology; D017403:In Situ Hybridization; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D050982:GATA1 Transcription Factor; D009687:Nuclear Proteins; D029961:Zebrafish Proteins; C494691:gata1a protein, zebrafish