Transcriptional repressors can be characterized by their range of action on promoters and enhancers. Short-range repressors interact over distances of 50-150 bp to inhibit, or quench, either upstream activators or the basal transcription complex. In contrast, long-range repressors act over several kilobases to silence basal promoters. We describe recent progress in characterizing the functional properties of one such long-range element in the Drosophila embryo and discuss the contrasting types of gene regulation that are made possible by short-and long-range repressors.Complex patterns of gene expression in the Drosophila embryo are specified by spatially localized activators and repressors. Mechanisms of transcriptional activation are beginning to be elucidated, but repression mechanisms are still poorly understood. A combination of genetic, molecular, and biochemical approaches have begun to address this issue. Several types of transcriptional repression have been proposed (1, 2), including direct competition of repressors and activators for common binding sites to DNA, local "quenching" of upstream activators or the basal transcription complex, and long-range interactions between repressors and the basal apparatus. The emerging picture is that some factors mediate "short-range" repression, interfering with transcriptional activators bound within 50-150 bp, whereas other "long-range" repressors are capable of interfering with promoter function over long distances (see Fig. 1). As we discuss below, one such long-range repressor complex, the ventral repression element (VRE) from the zerknullt (zen) gene, appears to silence the transcription complex over a distance of several kilobases. Drosophila promoters are often modular and contain a series of nonoverlapping enhancers, which function independently of one another to generate composite patterns of gene expression. The segmentation gene, even-skipped (eve) contains a modular promoter. It encodes a homeodomain protein that is essential for the subdivision of the embryo into a repeating series of body segments (3,4). eve is transcribed in a series of seven transverse stripes along the length of precellular embryos, foreshadowing overt segmentation of the germ band by several hours (5). The expression of at least some of the stripes are regulated by separate enhancers in the eve promoter region. For example, stripe 3 is regulated by a 500-bp enhancer located -3 kb upstream of the eve transcription start site (6). In contrast, stripe 2 is regulated by a separate 500-bp enhancer located -1 kb from the start site. The stripe 2 and stripe 3 enhancers are separated by a 1.7-kb "spacer" sequence in the eve promoter region. A major goal of our recent studies has been to determine how these two enhancers function independently of one another to generate a multistripe pattern of expression in early embryos. Short-range transcriptional repression appears to account for enhancer autonomy in a modular promoter. Repressors bound to a given enhancer do not interfere wit...