Zhx2 (zinc fingers and homeoboxes 2) regulates major urinary protein gene expression in the mouse liver

Jieyun Jiang, Kate Townsend Creasy, Justin Purnell, Martha L. Peterson, Brett T. Spear

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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. Zhx2 is located on chromosome 15, and a natural hypomorphic mutation in the BALB/cJ Zhx2 allele 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 with in vitro assays, 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.

Original languageEnglish
Pages (from-to)6765-6774
Number of pages10
JournalJournal of Biological Chemistry
Volume292
Issue number16
DOIs
StatePublished - Apr 21 2017

Bibliographical note

Funding Information:
This work is supported by Public Health Service Grants R01DK074816 (to B. T. S.), P20RR021954 (to B. T. S.), and T32DK007778 (to K. T. C.) and National Science Foundation Grant MCB-1158234 (to M. L. P.).

Publisher Copyright:
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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