A cis-regulatory map of the Drosophila genome

Elements of gene function Three papers in this issue of Nature report on the modENCODE initiative, which aims to characterize functional DNA elements in the fruitfly Drosophila melanogaster and the roundworm Caenorhabditis elegans . Kharchenko et al . present a genome-wide chromatin landscape of the fruitfly, based on 18 histone modifications. They describe nine prevalent chromatin states. Integrating these analyses with other data types reveals individual characteristics of different genomic elements. Graveley et al . have used RNA-Seq, tiling microarrays and cDNA sequencing to explore the transcriptome in 30 distinct developmental stages of the fruitfly. Among the results are scores of new genes, coding and non-coding transcripts, as well as splicing and editing events. Finally, Nègre et al . have produced a map of the regulatory part of the fruitfly genome, defining a vast array of putative regulatory elements, such as enhancers, promoters, insulators and silencers. As part of the modENCODE initiative, which aims to characterize functional DNA elements in D. melanogaster and C. elegans , this study created a map of the regulatory part of the fruitfly genome. On the basis of the developmental dynamics of chromatin modifications, polymerase and transcription factor occupancy this work defines a vast array of putative regulatory elements, such as enhancers, promoters, insulators and silencers. This resource represents the first attempt at a comprehensive annotation of cis -regulatory elements in a metazoan genome. Systematic annotation of gene regulatory elements is a major challenge in genome science. Direct mapping of chromatin modification marks and transcriptional factor binding sites genome-wide 1 , 2 has successfully identified specific subtypes of regulatory elements 3 . In Drosophila several pioneering studies have provided genome-wide identification of Polycomb response elements 4 , chromatin states 5 , transcription factor binding sites 6 , 7 , 8 , 9 , RNA polymerase II regulation 8 and insulator elements 10 ; however, comprehensive annotation of the regulatory genome remains a significant challenge. Here we describe results from the modENCODE cis -regulatory annotation project. We produced a map of the Drosophila melanogaster regulatory genome on the basis of more than 300 chromatin immunoprecipitation data sets for eight chromatin features, five histone deacetylases and thirty-eight site-specific transcription factors at different stages of dev