The impact of epigenetics on DNA-DNA interactions

It has become clear that DNA-DNA interactions are an important component of gene regulation and of the genetics of complex traits. The impact of DNA variation of these interactions is less well understood. This project will characterise two important loci, the major histocompatibility locus (MHC) and the imprinted H19/Igf2 locus in mice. These loci play key roles in immunity and growth and serve as models for the rest of the genome.

We will use Capture-C sequencing to assay DNA-DNA interactions between sites within these two loci and the rest of the genome, and CTCF-binding genome-wide, in two divergent in-bred strains and in reciprocal crosses of these two strains. We will repeat these assays in knockout mice. The experiment will tell us which genome-wide loci  interact with these loci. In particular, we will be able to test a prediction from our previous work that physical interactions occur between the MHC and H19/Igf2, and that genetic perturbations at the loci disturb these interactions.

These experiments will provide important proofs of principle of links between imprinted loci and the MHC.