title: Clustered arrangement of winged helix genes fkh-6 and MFH-1: possible implications for mesoderm development.
abstract: The 'winged helix' or 'forkhead' transcription factor gene family is defined by a common 100 amino acid DNA binding domain which is a variant of the helix-turn-helix motif. Here we describe the structure and expression of the mouse fkh-6 and MFH-1 genes. Both genes are expressed in embryonic mesoderm from the headfold stage onward. Transcripts for both genes are localised mainly to mesenchymal tissues, fkh-6 mRNA is enriched in the mesenchyme of the gut, lung, tongue and head, whereas MFH-1 is expressed in somitic mesoderm, in the endocardium and blood vessels as well as the condensing mesenchyme of the bones and kidney and in head mesenchyme. Both genes are located within a 10 kb region (in mouse chromosome 8 at 5.26 +/- 2.56 cM telomeric to Actsk1. The close physical linkage of these two winged helix genes is conserved in man, where the two genes map to chromosome 16q22-24. This tandem arrangement suggests the common use of regulatory mechanisms. The fkh-6/MFH-1 locus maps close to the mouse mutation amputated, which is characterised by abnormal development of somitic and facial mesoderm. Based on the expression patterns we suggest that a mutation in MFH-1, not fkh-6 is the possible cause for the amputated phenotype.
authors.affiliation: Division of Molecular Biology of the Cell I, German Cancer Research Centre, Heidelberg, Germany.
authors.forename: K H
authors.initials: KH
authors.lastname: Kaestner
authors.forename: S C
authors.initials: SC
authors.lastname: Bleckmann
authors.forename: A P
authors.initials: AP
authors.lastname: Monaghan
authors.forename: J
authors.initials: J
authors.lastname: Schlöndorff
authors.forename: A
authors.initials: A
authors.lastname: Mincheva
authors.forename: P
authors.initials: P
authors.lastname: Lichter
authors.forename: G
authors.initials: G
authors.lastname: Schütz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D051858:Forkhead Transcription Factors; D015870:Gene Expression; D005807:Genes, Overlapping; D006801:Humans; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; C491001:FOXL1 protein, human; D051858:Forkhead Transcription Factors; C099993:Foxl1 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; C082078:mesenchyme fork head 1 protein; D004247:DNA