Barx2 functions through distinct corepressor classes to regulate hair follicle remodeling.
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.
Olson
Lorin E
LE
Howard Hughes Medical Institute, Biomedical Sciences Graduate Program, University of California at San Diego School of Medicine, La Jolla, CA 92093-0648, USA.
Zhang
Jie
J
Taylor
Havilah
H
Rose
David W
DW
Rosenfeld
Michael G
MG
D000818:Animals; D002454:Cell Differentiation; D020869:Gene Expression Profiling; D018859:Hair Follicle / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D012097:Repressor Proteins / Q000502:physiology*; D012867:Skin / Q000378:metabolism
C105160:Barx2 protein, mouse; D018398:Homeodomain Proteins; D012097:Repressor Proteins
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