Web-based tools and approaches to study long-range gene regulation in Metazoa

Regulatory elements can affect specific genes from megabase distances, often from within or beyond unrelated neighbouring genes. The task of computational charting of regulatory inputs in the genome can be approached from several directions. Typically, computational identification of putative regulatory elements for a gene of interest requires tools that will aid in estimating the extent of the (potentially vast) genomic region around the gene that is likely to contain regulatory elements, as well as tools for the identification and characterization of individual elements. Conversely, starting from a putative regulatory element or a regulatory variation in a non-coding region, one often wants to associate the regulatory element with the correct target gene(s). The design of tools for these purposes relies on the remarkably high level of sequence conservation of thousands of regulatory enhancers, their strong tendency to cluster around their target genes, as well as a constrained range of functional categories of the corresponding target genes, many of which are developmental regulators. Additional evolutionary information, such as conservation of synteny, and a growing body of functional genomic and epigenomic data are being rapidly added to established and emerging tools for studying developmental regulation and cross-species conservation to provide new functional insights into the roles of these regions. In this article, we give an overview of the functionality available in general purpose and new/specialized web tools for the above tasks, and discuss current and future developments in the field.