Molecular and Cellular Endocrinology 216 (2004) 15–22 Epididymis-specific promoter-driven gene targeting: a new approach to control epididymal function? Kichiya Suzuki a,c,1 , Joel Drevet d , Barry T. Hinton e , Ilpo Huhtaniemi f , Jean-Jacques Lareyre g , Robert J. Matusik b,c , Eric Pons d , Matti Poutanen h , Petra Sipilä h , Marie-Claire Orgebin-Crist a,c,∗ a Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA b Department of Urologic Surgery, Vanderbilt University School of Medicine, Nashville, TN 37232, USA c Center for Reproductive Biology Research, Vanderbilt University School of Medicine, Nashville, TN 37232, USA d Department of Biology, Blaise Pascal University, CNRS UMR 6547 GEEM, Reproduction and Development, 63177 Aubière Cedex, France e Department of Cell Biology, University of Virginia Health Sciences Center, Charlottesville, VA, USA f Institute of Reproductive and Developmental Biology (IRDB), Faculty of Medicine, Imperial College, London W12 ONN, UK g INRA SCRIBE, Campus de Beaulieu, 35042 Rennes, France h Department of Physiology, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland 1. Introduction In the normal course of events, mammalian spermato- zoa acquire the capacity to move forward and fertilize in the epididymis. A distinct feature of this organ is that it displays a highly regionalized pattern of gene expression such that spermatozoa progressing through the epididymis encounter a succession of different luminal environments (Orgebin-Crist, 1996; Cornwall et al., 2002). This tissue-, region-, and cell-specific pattern of gene expression is crit- ical for the maintenance of a fully functional epididymis. Disrupting the process would provide an ideal approach to male contraception, since it would not interfere with testic- ular endocrine output or sperm production. To achieve this purpose, it is essential to understand the specific mechanisms involved in the control of tissue-, region-, and cell-specific gene expression in the epididymis. 2. Regionalized gene expression in the epididymis The epididymis can be divided into several distinct re- gions based on morphology and the expression of a unique set of genes. Initial studies on gene expression revealed a simple pattern of expression of certain genes in each epi- ∗ Corresponding author. Tel.: +1-615-322-7484; fax: +1-615-343-7797. E-mail address: m-c.orgebin-crist@vanderbilt.edu (M.-C. Orgebin-Crist). 1 Co-corresponding author. didymal region. For example, some genes are expressed exclusively in one region but not the other and some genes appear to be expressed throughout the entire length of the epididymis (Cornwall et al., 2002; Kirchhoff, 2002; Dacheux and Dacheux, 2002). Although this information is important and useful to our understanding of epididy- mal gene expression, it is also limiting in that it does not provide much insight into the purpose, the mechanisms by which regionalized gene expression occurs, and why and how gene expression is maintained. Maybe the expression of a unique set of genes sets up segments/regions along the epididymal duct. One might also envisage a more complex scenario in which sets of genes are expressed within each segment/region and each gene is regulated by different groups of enhancers and repressors. Hence, each region may well express the same gene, but its level of expression in combination with the expression of other genes, defines that segment/region of the epididymis. The idea of combinatorial control of gene expression, although not new, is only begin- ning to be appreciated and provides an attractive framework to understand the mechanisms underlying region-specific gene expression at the level of transcriptional regulation. 3. Combinatorial control of gene expression In multicellular organisms, the molecular mechanisms de- termining tissue-specific (TS) gene expression are in place at the onset of development, since a single cell, the fertil- ized egg, divides repeatedly to produce the many different cell types of the body. These cells share the same genome, 0303-7207/$ – see front matter © 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.mce.2003.10.070