In Drosophila, the morphogen Dpp patterns developing structures by directly regulating the expression of its target genes, which it also indirectly regulates by downregulating the transcription of the nuclear repressor brinker (brk). On , Yao et al. describe the intricate way in which multiple modular brk promoter elements generate an inverse brk expression gradient in response to the Dpp gradient. The promoter region of brk, they report, contains multiple compact modules, each of which contains one or more binding sites for the Schnurri/Mad/Medea (SMM) complex (which mediates the repression of some Dpp target genes) linked to regions that activate brk transcription. Because the SMM complex represses these activator regions in a distance-dependent manner, each module responds autonomously to Dpp signalling. However, unlike other modular promoters (for example, the promoter in the segmentation gene eve), the outputs from the regulatory modules in brk are integrated to generate the final brkexpression pattern. This unique promoter organisation, the researchers suggest, ensures a robust and precise response to Dpp signalling.
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