Characterization of Lef-1 promoter segments that facilitate inductive developmental expression in skin

TY - JOUR

T1 - Characterization of Lef-1 promoter segments that facilitate inductive developmental expression in skin

AU - Liu, Xiaoming

AU - Driskell, Ryan R

AU - Luo, Meihui

AU - Abbott, Duane

AU - Filali, Mohammed

AU - Cheng, Ningli

AU - Sigmund, Curt D

AU - Engelhardt, John F

PY - 2004/8

Y1 - 2004/8

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Division

KW - DNA-Binding Proteins

KW - Female

KW - Gene Expression Regulation, Developmental

KW - Genes, Reporter

KW - Hair Follicle

KW - Introns

KW - Lac Operon

KW - Lymphoid Enhancer-Binding Factor 1

KW - Male

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Pregnancy

KW - Promoter Regions, Genetic

KW - Proto-Oncogene Proteins

KW - Sebaceous Glands

KW - Transcription Factors

KW - Vibrissae

KW - Wnt Proteins

KW - beta-Galactosidase

U2 - 10.1111/j.0022-202X.2004.23201.x

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

M3 - Article

C2 - 15245424

SN - 0022-202X

VL - 123

SP - 264

EP - 274

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

IS - 2

ER -