Charting the regulatory landscape of the mouse genome in vivo

Abstract

Background Over the past years it has become apparent that a substantial part of mammalian gene regulation is achieved through the concerted action of long-range elements. Technical advances have greatly improved our ability to identify such elements, but still little is known about how they regulate gene expression mechanistically. It is particularly unclear to what extent genomic context influences the activity of regulatory elements, and therefore how authentically in vitro or transgene assays represent the actual activity of such elements. To characterise the regulatory architecture of genomic loci in vivo, we have developed GROMIT (Genome Regulatory Organisation Mapping with Integrated Transposons) [1]. GROMIT relies on the controlled mobilisation of a Sleeping Beauty transposon to distribute a lacZ reporter gene, acting as a regulatory sensor, throughout the mouse genome. The sensor integrates into the genome, without disrupting endogenous gene expression, and the precise location of insertions can be mapped.