title: Zhx2 (zinc fingers and homeoboxes 2) regulates major urinary protein gene expression in the mouse liver.
abstract: The mouse major urinary proteins (Mups) are encoded by a large family of highly related genes clustered on chromosome 4. Mups, synthesized primarily and abundantly in the liver and secreted through the kidneys, exhibit male-biased expression. Mups bind a variety of volatile ligands; these ligands, and Mup proteins themselves, influence numerous behavioral traits. Although urinary Mup protein levels vary between inbred mouse strains, this difference is most pronounced in BALB/cJ mice, which have dramatically low urinary Mup levels; this BALB/cJ trait had been mapped to a locus on chromosome 15. We previously identified Zhx2 (zinc fingers and homeoboxes 2) as a regulator of numerous liver-enriched genes.Zhx2is located on chromosome 15, and a natural hypomorphic mutation in the BALB/cJZhx2allele dramatically reduces Zhx2 expression. Based on these data, we hypothesized that reduced Zhx2 levels are responsible for lower Mup expression in BALB/cJ mice. Using both transgenic and knock-out mice along within vitroassays, our data show that Zhx2 binds Mup promoters and is required for high levels of Mup expression in the adult liver. In contrast to previously identified Zhx2 targets that appear to be repressed by Zhx2, Mup genes are positively regulated by Zhx2. These data identify Zhx2 as a novel regulator of Mup expression and indicate that Zhx2 activates as well as represses expression of target genes.
authors.affiliation: From the Department of Microbiology, Immunology, and Molecular Genetics, jieyun.jiang2@uky.edu.
authors.forename: Jieyun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Pharmacology and Nutritional Sciences, and.
authors.forename: Kate Townsend
authors.initials: KT
authors.lastname: Creasy
authors.affiliation: From the Department of Microbiology, Immunology, and Molecular Genetics.
authors.forename: Justin
authors.initials: J
authors.lastname: Purnell
authors.affiliation: From the Department of Microbiology, Immunology, and Molecular Genetics.|Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40536.
authors.forename: Martha L
authors.initials: ML
authors.lastname: Peterson
authors.affiliation: From the Department of Microbiology, Immunology, and Molecular Genetics, bspear@uky.edu.|Department of Pharmacology and Nutritional Sciences, and.|Markey Cancer Center, University of Kentucky College of Medicine, Lexington, Kentucky 40536.
authors.forename: Brett T
authors.initials: BT
authors.lastname: Spear
mesh_terms: D000483:Alleles; D000818:Animals; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D057809:HEK293 Cells; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008024:Ligands; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011506:Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D002843:Chromatin; D018398:Homeodomain Proteins; D008024:Ligands; D011506:Proteins; D014157:Transcription Factors; C476826:ZHX2 protein, human; C481543:Zhx2 protein, mouse; C035737:major urinary proteins
keywords: ChiP; development; hepatocyte; mouse genetics; transcription