title: 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.
authors.affiliation: Howard Hughes Medical Institute, Biomedical Sciences Graduate Program, University of California at San Diego School of Medicine, La Jolla, CA 92093-0648, USA.
authors.forename: Lorin E
authors.initials: LE
authors.lastname: Olson
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Havilah
authors.initials: H
authors.lastname: Taylor
authors.forename: David W
authors.initials: DW
authors.lastname: Rose
authors.forename: Michael G
authors.initials: MG
authors.lastname: Rosenfeld
mesh_terms: 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
chemical_list: C105160:Barx2 protein, mouse; D018398:Homeodomain Proteins; D012097:Repressor Proteins
references.citation: FASEB J. 2000 Apr;14(5):752-60
references.pmid: 10744631
references.citation: Methods Enzymol. 1995;254:3-20
references.pmid: 8531694
references.citation: Genes Dev. 2000 May 1;14(9):1048-57
references.pmid: 10809664
references.citation: EMBO J. 2000 May 15;19(10):2292-303
references.pmid: 10811620
references.citation: Hum Mol Genet. 2000 May 22;9(9):1443-52
references.pmid: 10814725
references.citation: Gene. 2000 May 16;249(1-2):1-16
references.pmid: 10831834
references.citation: Gene. 2000 May 30;250(1-2):171-80
references.pmid: 10854790
references.citation: EMBO J. 2000 Aug 15;19(16):4342-50
references.pmid: 10944117
references.citation: J Invest Dermatol. 2000 Oct;115(4):753-6
references.pmid: 10998155
references.citation: Cell. 2000 Sep 15;102(6):753-63
references.pmid: 11030619
references.citation: Physiol Rev. 2001 Jan;81(1):449-494
references.pmid: 11152763
references.citation: Cell. 2001 Mar 23;104(6):861-73
references.pmid: 11290324
references.citation: Development. 2001 May;128(9):1547-58
references.pmid: 11290294
references.citation: J Biol Chem. 2001 Apr 27;276(17):14482-9
references.pmid: 11278942
references.citation: Trends Mol Med. 2001 Jul;7(7):293-301
references.pmid: 11425637
references.citation: J Invest Dermatol. 2001 Jul;117(1):3-15
references.pmid: 11442744
references.citation: Genes Dev. 2001 Jul 1;15(13):1688-705
references.pmid: 11445543
references.citation: Dev Cell. 2001 Jul;1(1):13-25
references.pmid: 11703920
references.citation: Genes Dev. 2001 Dec 1;15(23):3193-207
references.pmid: 11731482
references.citation: Development. 2003 Jan;130(2):379-89
references.pmid: 12466204
references.citation: J Invest Dermatol. 2003 Jan;120(1):14-9
references.pmid: 12535193
references.citation: J Biol Chem. 2003 Mar 7;278(10):8269-78
references.pmid: 12486129
references.citation: EMBO J. 2003 Mar 17;22(6):1336-46
references.pmid: 12628926
references.citation: J Invest Dermatol. 2003 May;120(5):715-27
references.pmid: 12713572
references.citation: J Biol Chem. 2003 Jul 11;278(28):26120-6
references.pmid: 12714603
references.citation: J Invest Dermatol. 2003 Aug;121(2):219-30
references.pmid: 12880412
references.citation: Science. 2004 Jan 16;303(5656):359-63
references.pmid: 14671312
references.citation: Cell. 2004 Feb 20;116(4):511-26
references.pmid: 14980219
references.citation: Mol Cell Biol. 2004 Apr;24(8):3337-46
references.pmid: 15060155
references.citation: Cell. 1994 Sep 23;78(6):1017-25
references.pmid: 7923352
references.citation: EMBO J. 1995 Nov 1;14(21):5216-23
references.pmid: 7489711
references.citation: Development. 1996 Oct;122(10):3141-50
references.pmid: 8898227
references.citation: Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2632-7
references.pmid: 9122247
references.citation: Am J Pathol. 1997 Jun;150(6):1959-75
references.pmid: 9176390
references.citation: Genes Dev. 1998 Jan 1;12(1):11-20
references.pmid: 9420327
references.citation: Genes Dev. 1998 Jul 1;12(13):1931-40
references.pmid: 9649497
references.citation: Dev Biol. 1998 Jul 15;199(2):216-25
references.pmid: 9698441
references.citation: Nature. 1998 Sep 17;395(6699):301-6
references.pmid: 9751061
references.citation: Biochem Biophys Res Commun. 1999 May 10;258(2):374-8
references.pmid: 10329394
references.citation: N Engl J Med. 1999 Aug 12;341(7):491-7
references.pmid: 10441606
references.citation: J Biol Chem. 2000 Apr 14;275(15):11050-7
references.pmid: 10753908
references.citation: J Biol Chem. 1994 Dec 23;269(51):32551-7
references.pmid: 7798257
references.citation: Mech Dev. 1995 May;51(1):3-15
references.pmid: 7669690
references.citation: Proc Natl Acad Sci U S A. 2004 Nov 9;101(45):15955-60
references.pmid: 15520371