Retroviral integration sites (RIS) mark cis-regulatory elements

Transcription in multicellular eukaryotic organisms involves an elaborate orchestration of the core promoter and cis-regulatory elements to drive spatiotemporally and quantitatively correct gene expression. Unlike promoters found immediately upstream of protein-coding genes, the positions of distally located cis-regulatory elements relative to a gene of interest are difficult to define. As such, the identification and characterization of these regulatory elements has proved to be challenging. To this end, we propose a combinatorial in silico approach involving retroviral integration sites (RIS) mapping together with predicted matrix attachment regions (MARs) mapping and an already well-established comparative genomics approach, to enhance the prediction of potential cis-regulatory elements. Predicted elements can be validated by further investigations to ascertain their functions. In view of the abundance of electronically available RIS information, RIS mapping has an unrealized potential to aid in the discovery of novel cis-regulatory elements.