Bessa, J., Luengo, M., Rivero-Gil, S., Ariza-Cosano, A., Maia, A.H., Ruiz-Ruano, F.J., Caballero, P., Naranjo, S., Carvajal, J.J., and Gómez-Skarmeta, J.L. (2014) A mobile insulator system to detect and disrupt cis-regulatory landscapes in vertebrates. Genome research. 24(3):487-95.
In multicellular organisms, cis-regulation controls gene expression in space and time. Despite the essential implication
of cis-regulation in development and evolution of organisms and in human diseases, our knowledge about regulatory sequences
largely derives from analyzing their activity individually and outside their genomic context. Indeed, the contribution of
these sequences to the expression of their target genes in their genomic context is still largely unknown. Here we present
a novel genetic screen designed to visualize and interrupt gene regulatory landscapes in vertebrates. In this screen, based
on the random insertion of an engineered Tol2 transposon carrying a strong insulator separating two fluorescent reporter
genes, we isolated hundreds of zebrafish lines containing insertions that disrupt the cis-regulation of tissue specific expressed
genes. We therefore provide a new easy-to-handle tool that will help to disrupt and chart the regulatory activity spread through
the vast non-coding regions of the vertebrate genome.