Faculty Collaboration Database

Characterization of Lef-1 promoter segments that facilitate inductive developmental expression in skin. J Invest Dermatol 2004 Aug;123(2):264-74

Date

07/13/2004

Pubmed ID

15245424

Pubmed Central ID

PMC1803077

DOI

10.1111/j.0022-202X.2004.23201.x

Scopus ID

2-s2.0-3242675802 (requires institutional sign-in at Scopus site)   29 Citations

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.

Author List

Liu X, Driskell RR, Luo M, Abbott D, Filali M, Cheng N, Sigmund CD, Engelhardt JF

Author

Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cell Division
DNA-Binding Proteins
Female
Gene Expression Regulation, Developmental
Genes, Reporter
Hair Follicle
Introns
Lac Operon
Lymphoid Enhancer-Binding Factor 1
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Pregnancy
Promoter Regions, Genetic
Proto-Oncogene Proteins
Sebaceous Glands
Transcription Factors
Vibrissae
Wnt Proteins
beta-Galactosidase