Abdominal B gene (Abd-B) and directs a broad band of expression in the presumptive abdomen of gastrulating

Tissueand developmental stage-specific gene activation in higher eukaryotes depends on interactions between two classes of cis-regulatory DNA elements, the basal promoter where the transcription complex assembles, and the more distally located enhancers which interact with regulatory proteins (Burley and Roeder, 1996; Carey, 1998; Gray and Levine, 1996; Hansen et al., 1997; Small and Levine, 1991; Thanos and Maniatis, 1995; Verrijzer and Tjian, 1996). The relative independence of enhancer action regarding distance and orientation to the promoter presents a particular problem for the specificity of regulation among closely linked genes, such as those found in homeotic gene complexes (Gindhart et al., 1995; Karch et al., 1985; Krumlauf, 1994). Recent studies suggest that two distinct mechanisms specify promoter-enhancer interactions in eukaryotic gene complexes. Enhancer specificity may be determined by competition among multiple promoters through which the most preferred promoter(s) preclude others (Choi and Engel, 1988; Corbin and Maniatis, 1989; Foley and Engel, 1992; Sharpe et al., 1998; Walker et al., 1997). This is well illustrated by the developmental switch of the vertebrate βglobin genes in which two cis-linked ε and β globin promoters compete for a shared β/ε enhancer. During the embryonic stage, the ε gene promoter out-competes the β gene promoter and is preferentially activated by the β/ε enhancer. In adults, binding of adult-specific transcription factors near the basal promoter of the β gene augments the enhancer-β promoter interaction, resulting in activation of the β gene and concomitant shut-off of the ε gene (Foley and Engel, 1992). Core promoter sequences have been shown to influence the ability of promoters to compete for a given enhancer (Merli et al., 1996; Ohtsuki et al., 1998). Specifically, the contribution of core sequences to the promoter competitiveness has been shown with two early Drosophila enhancers, AE1 and IAB5. The autoregulatory enhancer (AE1) of the fushi tarazu gene (ftz) directs the expression in seven transverse stripes during germ band extension in Drosophila embryogenesis. AE1 selectively activates ftz but not the neighboring homeotic gene Sex combs reduced (Scr), in spite of its intergenic position and comparable distance from both promoters (Hiromi et al., 1985; LeMotte et al., 1989; Ohtsuki et al., 1998; Pick et al., 1990; Schier and Gehring, 1993). The AE1 promoter specificity could be determined by the differences in the basal promoters of the two genes: whereas the ftz promoter contains a canonical TATA box, the Scr promoter contains no optimally defined core promoter motifs such as the TATA sequence, initiator (INI) or downstream promoter element (DPE; Burke and Kadonaga, 1996; Kutach and Kadonaga, 2000; Smale, 1997). The infraabdominal 5 (IAB5) enhancer interacts specifically with the Abdominal B gene (Abd-B) and directs a broad band of expression in the presumptive abdomen of gastrulating embryos. Both AE1 and IAB5 contain binding sites for the FTZ activator. In transgenic Drosophila embryos, AE1 or IAB5 placed between two divergently transcribed reporter genes preferentially activates transcription from the TATA 4339 Development 128, 4339-4347 (2001) Printed in Great Britain © The Company of Biologists Limited 2001 DEV5446