title: Structure of the mouse Stat 3/5 locus: evolution from Drosophila to zebrafish to mouse.
abstract: Signal transducers and activators of transcription (Stat) are transcription factors that can be activated by many cytokines. While Drosophila contains only one Stat (d-Stat), mammals contain seven, with STATs 3, 5a, and 5b being the closest functional relatives. To understand the evolutionary relationship between d-Stat and vertebrate STATs 3 and 5, we isolated, sequenced, and analyzed the zebrafish Stat3 (z-Stat3) gene and a 500-kb region spanning mouse chromosome 11, 60.5 cM containing three Stat genes (m-Stats). Within this region we identified the genes encoding m-Stats 3, 5a, and 5b, Cnp1, Hcrt/Orexin, Ptrf, GCN5, mDj11, and four new genes. The 5' ends of the m-Stat5a and m-Stat5b genes are juxtaposed to each other, and the 3' ends of the m-Stat3 and Stat5a genes face each other. While the m-Stat5a and m-Stat3 genes have one promoter each, which are active in many tissues, the m-Stat5b gene acquired two distinct promoters. The distal promoter is expressed ubiquitously, and transcription from the proximal promoter is restricted to liver, muscle, and mammary tissue. Through a comparison of exon-intron boundaries from the m-Stat3, m-Stat5a, and m-Stat5b, z-Stat3, and d-Stat genes, we deduced their evolutionary relationship. We propose that the Stat3 and Stat5 lineages are derived from the duplication of a common primordial gene and that d-Stat is a part of the Stat5 lineage.
authors.affiliation: Laboratory of Genetics and Physiology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 9000 Rockville Pike, Building 8, Room 101, Bethesda, Maryland 20892, USA.
authors.forename: K
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Y
authors.initials: Y
authors.lastname: Cui
authors.forename: G
authors.initials: G
authors.lastname: Riedlinger
authors.forename: P
authors.initials: P
authors.lastname: Robinson
authors.forename: J
authors.initials: J
authors.lastname: Lehoczky
authors.forename: L
authors.initials: L
authors.lastname: Zon
authors.forename: T
authors.initials: T
authors.lastname: Oka
authors.forename: K
authors.initials: K
authors.lastname: Dewar
authors.forename: L
authors.initials: L
authors.lastname: Hennighausen
mesh_terms: D000818:Animals; D001483:Base Sequence; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D004330:Drosophila / Q000235:genetics; D019143:Evolution, Molecular; D005091:Exons; D007438:Introns; D051379:Mice; D008894:Milk Proteins; D008969:Molecular Sequence Data; D005810:Multigene Family; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; D017422:Sequence Analysis, DNA; D014018:Tissue Distribution; D015534:Trans-Activators / Q000235:genetics*; D015027:Zebrafish / Q000235:genetics; D029961:Zebrafish Proteins
chemical_list: D004268:DNA-Binding Proteins; D008894:Milk Proteins; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D050799:STAT5 Transcription Factor; C494087:Stat3 protein, mouse; C494093:Stat5a protein, mouse; C494096:Stat5b protein, mouse; D015534:Trans-Activators; D029961:Zebrafish Proteins; C494098:ihb394 protein, zebrafish; C494089:stat3 protein, zebrafish; C494099:stat5b protein, zebrafish