Tissue-specific expression of genes is achieved, at least in part, by the presence of specific sequences termed enhancer elements, usually located upstream of transcription initiation sites (39). Some of these elements represent binding sites for ubiquitous trans-acting factors which increase the expression of genes containing these binding sites in a number of different cell types, whereas other elements are apparently recognized by factors found only in specific cell types. It is these latter factors that contribute, at least in part, to the tissue-specific expression of genes.Negative regulation also has been reported to influence gene expression in specific cell types (24,45). Some, if not all, genes contain both positive enhancer elements and negative regulatory elements (NREs), which may act as binding sites for factors which inhibit gene expression, possibly by interfering with the binding of positively acting factors (1,2,38). In addition, a number of retroviral long terminal repeats (LTRs) have been shown to encode NREs which suppress transcription (5, 14, 37).The endogenous murine retrovirus mouse mammary tumor virus (MMTV) is expressed in several tissues (18). When transgenic mice were made by using reporter genes under the transcriptional control of the MMTV LTR, the transgenes were expressed in the same tissues as was the endogenous virus, namely, the epithelial cells of the mammary and salivary glands, lungs, kidneys, and seminal vesicles and the lymphoid cells of the spleen and thymus (9,26,41,42
