GATA Factors and Androgen Receptor Collaborate to Transcriptionally Activate the Rhox5 Homeobox Gene in Sertoli Cells

Mol Cell Biol. 2008 Apr;28(7):2138-53. doi: 10.1128/MCB.01170-07. Epub 2008 Jan 22.

Abstract

How Sertoli-specific expression is initiated is poorly understood. Here, we address this issue using the proximal promoter (Pp) from the Rhox5 homeobox gene. Its Sertoli cell-specific expression is achieved, in part, through a negative regulatory element that inhibits Pp transcription in non-Sertoli cell lines. Complementing this negative regulation is positive regulation conferred by four androgen-response elements (AREs) that interact with the androgen receptor (AR), a nuclear hormone receptor expressed at high levels in Sertoli cells. A third control mechanism is provided by a consensus GATA-binding site that is crucial for Pp transcription both in vitro and in vivo. Several lines of evidence suggested that GATA factors and AR act cooperatively to activate Pp transcription: (i) the GATA-binding site crucial for Pp transcription is in close proximity to two of the AREs, (ii) GATA and AR form a complex with the Pp in vitro, (iii) overexpression of GATA factors rescued expression from mutant Pp constructs harboring defective AREs, and (iv) incubation of a Sertoli cell line with testosterone triggered corecruitment of AR and GATA4 to the Pp. Collectively, our results suggest that the Rhox5 gene achieves Sertoli cell-specific transcription using a combinatorial strategy involving negative and cooperative positive regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • Cell Line
  • GATA Transcription Factors / physiology*
  • Genes, Homeobox*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Promoter Regions, Genetic / genetics*
  • Prostate-Specific Antigen / genetics
  • Protein Interaction Mapping
  • Receptors, Androgen / physiology*
  • Recombinant Fusion Proteins / physiology
  • Response Elements / genetics
  • Sertoli Cells / metabolism*
  • Testis / embryology
  • Testis / growth & development
  • Transgenes

Substances

  • GATA Transcription Factors
  • Receptors, Androgen
  • Recombinant Fusion Proteins
  • Prostate-Specific Antigen