Epididymis-specific promoter-driven gene targeting: A transcription factor which regulates epididymis-specific gene expression

Kichiya Suzuki, Xiuping Yu, Pierre Chaurand, Yoshihiko Araki, Jean Jacques Lareyre, Richard M. Caprioli, Robert J. Matusik, Marie Claire Orgebin-Crist

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

Abstract

Mammalian spermatozoa undergo several modification and finally acquire the ability to fertilize during epididymal transit. One of the distinct features of the epididymis is that it displays a highly regionalized pattern of gene expression. This tissue-, region-, and cell-specific pattern of gene expression is critical for the maintenance of a fully functional epididymis. One would hypothesize that disrupting this process provides an ideal approach to male contraception, since it would not interfere with testicular endocrine output or sperm production. To achieve this purpose, we studied a cluster of epididymis-specific lipocalin genes for understanding the specific mechanisms involved in the control of gene expression in the epididymis. We have identified six epididymis-specific lipocalin genes that are differently regulated and regionalized in the epididymis. Lipocalin 5 [Lcn5 or epididymal retinoic acid-binding protein (E-RABP)] is a member of this epididymis-specific lipocalin gene cluster, which binds hydrophobic molecules such as retinoic acid. We have previously shown that the 5 kb promoter fragment of the Lcn5 gene confers both androgen-dependent regulation and epididymis-specific gene expression in transgenic mice whereas 0.6 kb promoter fragment does not. To further narrow down the important cis-regulatory elements that regulate gene expression in the epididymis, we studied the Lcn5 promoter in both transgenic mice and immortalized epididymal cells. We have found that 1.8 kb promoter fragment of the Lcn5 gene was sufficient for tissue- and region-specific expression in transgenic mice, and that a transcription factor Forkhead box A2 (Foxa2) interacts with the androgen receptor and binds to the 100 bp fragment of the Lcn5 promoter between 1.2 and 1.3 kb. Our finding provides a framework for further analysis of the epididymal lipocalin gene regulation and modulated control of epididymis-specific expression.

Original languageEnglish
Pages (from-to)184-189
Number of pages6
JournalMolecular and Cellular Endocrinology
Volume250
Issue number1-2
DOIs
Publication statusPublished - 2006 May 16
Externally publishedYes

Keywords

  • Androgen
  • Epididymis
  • Gene cluster
  • Gene evolution
  • Gene regulation
  • Lipocalin
  • Transcription factor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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