title: Characterization of Lef-1 promoter segments that facilitate inductive developmental expression in skin.
abstract: Lymphoid Enhancer Factor 1 (Lef-1) is an important developmental transcription factor required for the inductive formation of several epithelial-derived organs including hair follicles. Inductive expression of Lef-1 mRNA is tightly regulated during embryo development, suggesting the involvement of a highly regulated promoter. In vitro analysis of the Lef-1 gene has demonstrated the existence of at least two spatially distinct promoters with multiple transcriptional start sites that are responsive to the canonical Wnt/beta-catenin pathway. Regions of the Lef-1 promoter required for inductive regulation in vivo, however, have yet to be determined. To this end, we utilized LacZ-reporter transgenic mice to define segments of the human Lef-1 promoter capable of reproducing mesenchymal- or epithelial-restricted transcriptional patterns of Lef-1 expression during hair and vibrissa follicle development. These studies have revealed that a 110 bp Wnt/beta-catenin-responsive element, contained within a minimal 2.5 kb Lef-1 promoter, plays an important role in regulating mesenchymal, and potentially epithelial, expression during follicle development in mouse embryos. This 2.5 kb Lef-1 promoter also demonstrated inductive mesenchymal expression during postnatal anagen stage hair-follicle cycling. Additionally, analysis of Lef-1 promoter expression revealed previously uncharacterized regions of endogenous Lef-1 expression seen in the sebaceous glands of vibrissa and hair follicles in transgenic lines harboring the minimal Lef-1 promoter and additional intronic sequences. In summary, these studies have begun to dissect the transcriptional diversity of the human Lef-1 promoter during the hair/vibrissa follicle and sebaceous gland formation.
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242-1109, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.forename: Ryan R
authors.initials: RR
authors.lastname: Driskell
authors.forename: Meihui
authors.initials: M
authors.lastname: Luo
authors.forename: Duane
authors.initials: D
authors.lastname: Abbott
authors.forename: Mohammed
authors.initials: M
authors.lastname: Filali
authors.forename: Ningli
authors.initials: N
authors.lastname: Cheng
authors.forename: Curt D
authors.initials: CD
authors.lastname: Sigmund
authors.forename: John F
authors.initials: JF
authors.lastname: Engelhardt
mesh_terms: D000818:Animals; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D018859:Hair Follicle / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D007438:Introns; D007763:Lac Operon; D051821:Lymphoid Enhancer-Binding Factor 1; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011247:Pregnancy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012627:Sebaceous Glands / Q000196:embryology / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics*; D014738:Vibrissae / Q000166:cytology / Q000196:embryology / Q000502:physiology; D051153:Wnt Proteins; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D051153:Wnt Proteins; D001616:beta-Galactosidase