Abstract
The "winged helix" or "forkhead" transcription factors comprise a large gene family whose members are defined by a common 100-amino acid DNA binding domain. Here we describe the structure and expression of the mouse fkh-2 gene, which encodes a protein of 48 kDa with high similarity to other winged helix transcription factors within the DNA binding region, but unique potential transactivation domains. The gene is encoded by a single exon and is expressed in headfold stage embryos in the notochord, the anterior neuroectoderm, and a few cells of the definite endoderm. This expression becomes restricted to the anteriormost portions of the invaginating foregut and the developing midbrain. From day 11.5 of gestation onward, fkh-2 transcripts are restricted to the midbrain and become progressively localized to the red nuclei as the sole site of expression. The fkh-2 gene maps to chromosome 19B and is a candidate gene for the mouse mutation mdf (muscle-deficient) which is characterized by nervous tremors and degeneration of the hindlimb muscles. Although the expression patterns of the fkh-2 gene and another winged helix protein, HNF-3 beta, are overlapping in early stages of gestation and although the promoter of the fkh-2 gene contains a HNF-3 binding site, we demonstrate that the activation of the fkh-2 gene is independent of HNF-3 beta.
Highlights
The “winged helix” or “forkhead” transcription factors comprise a large gene family whose members are defined by a common 100-amino acid DNA binding domain
The expression patterns of the fkh-2 gene and another winged helix protein, HNF3, are overlapping in early stages of gestation and the promoter of the fkh-2 gene contains a HNF-3 binding site, we demonstrate that the activation of the fkh-2 gene is independent of HNF-3
It should be noted that the fkh-2 protein contains no homology to the transactivation domains characterized for HNF-3 (Pani et al, 1992) and other winged helix proteins (reviewed in Lai et al (1993)), indicating the functional diversity of the winged helix gene family, in addition to the different intron/exon organization
Summary
The “winged helix” or “forkhead” transcription factors comprise a large gene family whose members are defined by a common 100-amino acid DNA binding domain. We describe the structure and expression of the mouse fkh-2 gene, which encodes a protein of 48 kDa with high similarity to other winged helix transcription factors within the DNA binding region, but unique potential transactivation domains. The “winged helix” or “forkhead” transcription factors comprise a large and growing gene family whose members are defined by a common 100-amino acid DNA binding domain. We report the detailed characterization of one of these genes, fkh-2, whose expression pattern suggests that it plays an important role in the regionalization of the foregut, notochord, and midbrain of mouse embryos
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