42C. M. Rodríguez et al. studies have demonstrated that the expression of these androgen-dependent proteins is controlled at the transcriptional level by androgen receptor via hormone response elements. Most studies have determined androgen dependence by examining gene expression before and after orchidectomy. The presence of an androgen response element (ARE) in the promoter region is an indicator that a gene may be regulated by androgens at transcription. The mouse CRISP-1 gene contains several motifs similar to those of an ARE consensus sequence (Schwidetzky et al., 1997). Nonetheless, further studies must be conducted to determine whether these putative AREs are indeed involved in the androgen-dependent expression of CRISP-1. Lareyre et al. (2000) identified two androgen-specific response regions within the 5Ј flanking region of the mE-RABP. Further experiments determined that only one of these regions, ARBS-1, was the major cis-element responsible for androgen responsiveness. Functional AREs are also present in the arMEP24 promoter (Ghyselinck et al., 1993) and the gpx5 promoter (Lareyre et al., 1997). Oestrogen-and retinoic acid-regulated genes have not been identified in the epididymis. However, oestrogen receptors may modulate the expression of genes involved in the regulation of fluid resorption in the efferent ductules. For example, oestrogens regulate the expression of aquaporin-1 (Fisher et al., 1998) but further studies must be conducted to determine whether this regulation takes place at transcription via oestrogen response elements.
Transcription factors as repressorsIn addition to acting as activators, transcription factors can also function as repressors of transcription initiation. For example, PEA3 has been shown to act as a repressor of GGT-IV (Lan et al., 1999) and gpx5 (Drevet et al., 1998) transcriptional activity. Specific domains present in transcription factors mediate repression of gene expression. The KRAB (Krüppel-associated box) transcription domain of the KOX1 protein is a conserved motif present in zinc finger proteins, and is responsible for suppressing transcription activation mediated by a number of transcription factors (Peng et al., 2000). The KRAB domain has been reported to repress the expression of oestrogen-regulated genes (de Haan et al., 2000).
Co-regulatorsThe transcriptional activity of SRs is modulated further by a number of proteins. Co-regulators, or more specifically, co-activators and co-repressors are proteins that cooperate with traditional transcription factors to promote or repress the expression of particular genes. Co-regulators do not bind to DNA, yet act as molecular bridges between the cisacting elements and the basal transcriptional machinery. Most of the studies on these molecules have been in the context of their modulation of steroid hormone receptor responses; however, co-regulators modulate the function of a wide range of transcriptional regulators. In the absence of ligand, steroid receptors associate with co-repressor proteins. These p...