KRAB-ZFPs and the establishment of lineage- and species-specific gene regulatory networks

KRAB-ZFPs are a family of proteins so numerous that it was unreasonable to study them on a large scale until recently. Through indirect studies of a common cofactor, they were known for their role in ensuring that invaders of viral origin residing in our genome remain dormant. My post-doctoral work showed where each human KRAB-ZFP binds in the genome although the biological role of most of them remains nebulous. We found significant evidence indicating that that they could influence regulation of cellular genes at a distance.

We will investigate this hypothesis and determine if they can help explain many of the differences that exist between species (for example, mouse and human). We also want to improve our understanding of how they can generate these differences by comparing how the same sequences evolved in many related species. We will pay special attention to variability between people, using new genome sequencing data.