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Barx2 functions through distinct corepressor classes to regulate hair follicle remodeling.

ABSTRACT: The hair-growth cycle, a complex biological system requiring coordinate alterations in gene expression and cellular behavior, provides a challenging model for investigating the interplay of specific transcriptional regulation events. Here we report that the Barx2 homeodomain factor serves as a regulator of hair follicle remodeling (catagen), and loss of Barx2 in mice causes a defect both in the initiation and progression of catagen, resulting in a protracted first catagen, and later, causing short hair in adult gene-deleted mice. Barx2 negatively regulates its own promoter, and our study highlights the role of Barx2 as a repressor in the skin that can, unexpectedly, functionally interact with two WD40-domain factors distantly related to the yeast corepressor Tup1. These two corepressors, transducin-like enhancer of split and transducin beta-like 1, function through distinct and independent interactions with Barx2 for the repression of gene targets, including the Barx2 gene itself, emphasizing the roles of complementary repression strategies in engrailed homology-1 motif-containing homeodomain factors. Together, our data suggest that the hair-remodeling defect of Barx2 mutant mice could be explained, in part, by failure to repress one or more critical target genes.

SUBMITTER: Olson LE

PROVIDER: S-EPMC553323 | biostudies-literature | 2005 Mar

REPOSITORIES: biostudies-literature

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Barx2 functions through distinct corepressor classes to regulate hair follicle remodeling.

Olson Lorin E LE Zhang Jie J Taylor Havilah H Rose David W DW Rosenfeld Michael G MG

Proceedings of the National Academy of Sciences of the United States of America 20050222 10

The hair-growth cycle, a complex biological system requiring coordinate alterations in gene expression and cellular behavior, provides a challenging model for investigating the interplay of specific transcriptional regulation events. Here we report that the Barx2 homeodomain factor serves as a regulator of hair follicle remodeling (catagen), and loss of Barx2 in mice causes a defect both in the initiation and progression of catagen, resulting in a protracted first catagen, and later, causing sho ...[more]

PMID: 15728386

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Project description:BackgroundHair follicles are an appendage of the vertebrate epithelium in the skin that arise from the embryonic ectoderm and regenerate cyclically during adulthood. Dermal papilla cells (DPCs) are the key dermal component of the hair follicle that directly regulate hair follicle development, growth and regeneration. According to recent studies, miRNAs play an important role in regulating hair follicle morphogenesis and the proliferation, differentiation and apoptosis of hair follicle stem cells.ResultsThe miRNA expression profile of the DPCs from Rex rabbits with different hair densities revealed 240 differentially expressed miRNAs (|log2(HD/LD)| > 1.00 and Q-value≤0.001). Among them, ocu-miR-205-5p was expressed at higher levels in DPCs from rabbits with low hair densities (LD) than in rabbits with high hair densities (HD), and it was expressed at high levels in the skin tissue from Rex rabbits (P < 0.05). Notably, ocu-miR-205 increased cell proliferation and the cell apoptosis rate, altered the progression of the cell cycle (P < 0.05), and modulated the expression of genes involved in the PI3K/Akt, Wnt, Notch and BMP signalling pathways in DPCs and skin tissue from Rex rabbits. It also inhibited the phosphorylation of the CTNNB1 and GSK-3β proteins, decreased the level of the noggin (NOG) protein, and increased the level of phosphorylated Akt (P < 0.05). A significant change in the primary follicle density was not observed (P > 0.05), but the secondary follicle density and total follicle density (P < 0.05) were altered upon interference with ocu-miR-205-5p expression, and the secondary/primary ratio (S/P) in the ocu-miR-205-5p interfered expression group increased 14 days after the injection (P < 0.05).ConclusionsIn the present study, ocu-miR-205 promoted the apoptosis of DPCs, altered the expression of genes and proteins involved in the PI3K/Akt, Wnt, Notch and BMP signalling pathways in DPCs and skin from Rex rabbits, promoted the transition of hair follicles from the growth phase to the regression and resting phase, and altered the hair density of Rex rabbits.

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Barx2 functions through distinct corepressor classes to regulate hair follicle remodeling.

Publications

Barx2 functions through distinct corepressor classes to regulate hair follicle remodeling.

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