GATA transcription factors are important regulators of both hematopoiesis (GATA-1/2/3) and cardiogenesis (GATA4
) in mammals. The transcriptional activities of the GATA proteins are modulated by their interactions with other
transcription factors and with transcriptional coactivators and repressors. Friend of GATA1 (FOG) is a zinc
finger protein that interacts with GATA1 and modulates its transcriptional activity in vitro and in vivo.
Svensson et al. (1999) described the molecular cloning and characterization of another FOG-related protein, FOG2, in
mouse. They found that FOG2 is a 1,151-amino acid nuclear protein that contains 8 zinc finger motifs that are
structurally related to those of FOG.
NCBI Summary:
The zinc finger protein encoded by this gene is a widely expressed member of the FOG family of transcription factors. The family members modulate the activity of GATA family proteins, which are important regulators of hematopoiesis and cardiogenesis in mammals. It has been demonstrated that the protein can both activate and down-regulate expression of GATA-target genes, suggesting different modulation in different promoter contexts. A related mRNA suggests an alternatively spliced product but this information is not yet fully supported by the sequence. [provided by RefSeq, Jul 2008]
General function
Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Germ cell development
Comment
Tevosian SG, et al 2002 reported that gonadal differentiation, sex determination and normal Sry
expression in mice require direct interaction between
transcription partners GATA4 and FOG2.
In mammals, Sry expression in the bipotential, undifferentiated gonad directs
the support cell precursors to differentiate as Sertoli cells, thus initiating
the testis differentiation pathway. In the absence of Sry, or if Sry is
expressed at insufficient levels, the, support cell precursors differentiate
as granulosa cells, thus initiating the ovarian pathway. The molecular
mechanisms upstream and downstream of Sry are not well understood. Mouse fetuses homozygous for a null
allele of Fog2 or homozygous for a targeted mutation in Gata4 (Gata4(ki)) that
abrogates the interaction of GATA4 with FOG co-factors exhibit abnormalities
in gonadogenesis. Sry transcript levels were significantly
reduced in XY Fog2(-/-) gonads at E11.5, which is the time when Sry expression
normally reaches its peak. In addition, three genes crucial for normal Sertoli
cell function (Sox9, Mis and Dhh) and three Leydig cell steroid biosynthetic
enzymes (p450scc, 3betaHSD and p450c17) were not expressed in XY Fog2(-/-) and
Gata(ki/ki) gonads, whereas Wnt4, a gene required for normal ovarian
development, was expressed ectopically. By contrast, Wt1 and Sf1, which are
expressed prior to Sry and necessary for gonad development in both sexes, were
expressed normally in both types of mutant XY gonads. These results indicate
that GATA4 and FOG2 and their physical interaction are required for normal
gonadal development.
Expression regulated by
Comment
Ovarian localization
Granulosa, Luteal cells
Comment
Laitinen MPE, et al 2000 reported that transcription factors GATA-4 and GATA-6 and a GATA family
cofactor, FOG-2, are expressed in human ovary and sex
cord-derived ovarian tumors.
Both human ovarian tissue samples and freshly isolated granulosa luteal (GL) cells derived from preovulatory
follicles of gonadotropin-treated women express GATA-4, GATA-6, and FOG-2
transcripts. The findings support a
role for GATA-binding proteins in human ovarian folliculogenesis.
Follicle stages
Preovulatory
Comment
Phenotypes
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: embryonic lethal Comment:Tevosian et al. (2000) disrupted the Fog2 gene in mice to define its requirement in vivo. Fog2 -/- mouse embryos died
at midgestation with a cardiac defect characterized by a thin ventricular myocardium, common atrioventricular canal,
and the tetralogy of Fallot malformation. Remarkably, coronary vasculature was absent in Fog2 -/- hearts
Species: mouse
Mutation name: None
type: None fertility: None Comment: Conditional ablation of Gata4 and Fog2 genes in mice reveals their distinct roles in mammalian sexual differentiation. Manuylov NL et al. Assembly of functioning testis and ovary requires a GATA4-FOG2 transcriptional complex. To define the separate roles for GATA4 and FOG2 proteins in sexual development of the testis we have ablated the corresponding genes in somatic gonadal cells. We have established that GATA4 is required for testis differentiation, for the expression of Dmrt1 gene, and for testis cord morphogenesis. While Sf1Cre-mediated excision of Gata4 permitted normal expression of most genes associated with embryonic testis development, gonadal loss of Fog2 resulted in an early partial block in male pathway and sex reversal. We have also determined that testis sexual differentiation is sensitive to the timing of GATA4 loss during embryogenesis. Our results now demonstrate that these two genes also have non-overlapping essential functions in testis development.