Androgen receptor binding to an androgen-responsive element in the promoter of the Srsf4 gene inhibits its expression in mouse Sertoli cells

Mol Reprod Dev. 2015 Dec;82(12):976-85. doi: 10.1002/mrd.22576. Epub 2015 Sep 3.

Abstract

The serine/arginine-rich splicing actor 4 (SRSF4) is essential for pre-mRNA splicing and can influence alternative-splice-site choice. Little is known about the specific function of this gene in the reproductive system, although a recent study identified a SRSF4 polymorphism significantly associated with a decreased risk of non-obstructive azoospermia in Chinese men. We previously found that the expression of Srsf4 was up-regulated in the testes of Sertoli-cell-selective androgen receptor knockout (S-Ar(-/y)) mice compared to wild-type mice using digital gene expression analysis. In this study, we confirmed and extended the selective gene expression data: SRSF4 was mainly located in the nucleus of Sertoli cells, and Srsf4 expression in the Sertoli-cell-derived cell line TM4 is down-regulation by testosterone. Moreover, androgen receptor directly binds the androgen-responsive element of the Srsf4 promoter. Taken together, these results demonstrate that Srsf4 is a direct downstream target of the androgen receptor in mouse Sertoli cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Gene Knockdown Techniques
  • Male
  • Mice
  • RNA-Binding Proteins / biosynthesis*
  • RNA-Binding Proteins / genetics
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Response Elements / physiology*
  • Sertoli Cells / cytology
  • Sertoli Cells / metabolism*
  • Testosterone / pharmacology

Substances

  • RNA-Binding Proteins
  • Receptors, Androgen
  • Testosterone