cis-regulatory modules

Deciphering the regulatory codes that dictate developmental and tissue-specific patterns of transcriptional control is a formidable challenge. In the January 22 Proceedings of the National Academy of Sciences, Berman et al. describe a computational approach to explore the grammar of cis-regulatory modules (Proc Natl Acad Sci USA 2002, 99:757-762). They focused on the Drosophila genome and searched for high, local densities of binding sites for multiple transcription factors (Bicoid, Caudal, Hunchback, Kruppel and Knirps) using position weight matrices. They identified clusters of binding sites that defined cis-regulatory modules implicated in developmental expression patterns. These clusters were located adjacent to genes exhibiting localized anterior-posterior expression. An accompanying paper by Markstein et al. describes a similar study using clusters of binding sites to identify novel targets genes for the Dorsal transcription factor (Proc Natl Acad Sci USA 2002, 99:763-768). Both reports highlight the value of combining in silico predictions of cis-regulatory modules with experimental confirmation of target gene networks.