title: The role and regulation of friend of GATA-1 (FOG-1) during blood development in the zebrafish.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Hematology, Brigham & Women's Hospital, Boston, MA 02115, USA.
authors.forename: Julio D
authors.initials: JD
authors.lastname: Amigo
authors.forename: Gabriele E
authors.initials: GE
authors.lastname: Ackermann
authors.forename: John J
authors.initials: JJ
authors.lastname: Cope
authors.forename: Ming
authors.initials: M
authors.lastname: Yu
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Cooney
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ma
authors.forename: Nathaniel B
authors.initials: NB
authors.lastname: Langer
authors.forename: Ebrahim
authors.initials: E
authors.lastname: Shafizadeh
authors.forename: George C
authors.initials: GC
authors.lastname: Shaw
authors.forename: Wyatt
authors.initials: W
authors.lastname: Horsely
authors.forename: Nikolaus S
authors.initials: NS
authors.lastname: Trede
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Davidson
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Barut
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Wojiski
authors.forename: David
authors.initials: D
authors.lastname: Traver
authors.forename: Tyler B
authors.initials: TB
authors.lastname: Moran
authors.forename: George
authors.initials: G
authors.lastname: Kourkoulis
authors.forename: Karl
authors.initials: K
authors.lastname: Hsu
authors.forename: John P
authors.initials: JP
authors.lastname: Kanki
authors.forename: Dhvanit I
authors.initials: DI
authors.lastname: Shah
authors.forename: Hui Feng
authors.initials: HF
authors.lastname: Lin
authors.forename: Robert I
authors.initials: RI
authors.lastname: Handin
authors.forename: Alan B
authors.initials: AB
authors.lastname: Cantor
authors.forename: Barry H
authors.initials: BH
authors.lastname: Paw
mesh_terms: 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
chemical_list: D050982:GATA1 Transcription Factor; D009687:Nuclear Proteins; D029961:Zebrafish Proteins; C494691:gata1a protein, zebrafish