title: The whn transcription factor encoded by the nude locus contains an evolutionarily conserved and functionally indispensable activation domain.
abstract: Mutations in the whn gene are associated with the phenotype of congenital athymia and hairlessness in mouse and rat. The whn gene encodes a presumptive transcription factor with a DNA binding domain of the forkhead/ winged-helix class. Two previously described null alleles encode truncated whn proteins lacking the characteristic DNA binding domain. In the rat rnu allele described here, a nonsense mutation in exon 8 of the whn gene was identified. The truncated whnrnu protein contains the DNA binding domain but lacks the 175 C-terminal amino acids of the wild-type protein. To facilitate the identification of functionally important regions in this region, a whn homolog from the pufferfish Fugu rubripes was isolated. Comparison of derived protein sequences with the mouse whn gene revealed the presence of a conserved acidic protein domain in the C terminus, in addition to the highly conserved DNA binding domain. Using fusions with a heterologous DNA binding domain, a strong transcriptional activation domain was localized to the C-terminal cluster of acidic amino acids. As the whnrnu mutant protein lacks this domain, our results indicate that a transactivation function is essential for the activity of the whn transcription factor.
authors.affiliation: Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Schüddekopf
authors.forename: M
authors.initials: M
authors.lastname: Schorpp
authors.forename: T
authors.initials: T
authors.lastname: Boehm
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D005075:Biological Evolution; D018389:Codon, Nonsense; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D005091:Exons; D005400:Fishes, Poisonous; D051858:Forkhead Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D010641:Phenotype; D051381:Rats; D011923:Rats, Nude; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D018389:Codon, Nonsense; D004268:DNA-Binding Proteins; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; C090140:Whn protein; D004247:DNA