The impact of epigenetics on DNA-DNA interactions (360G-Wellcome-109827_Z_15_Z)

It has become clear that DNA-DNA interactions are an important component of gene regulation and of complex trait genetics. 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 bet ween sites within these two loci and the rest of the genome, and CTCF-binding genome-wide, in two divergent inbred strains (C57BL/6J and CAST/EiJ), and in reciprocal crosses of these two strains. We will repeat these assays in reciprocal crosses of C57BL/6J and the knockout C57BL/6N-Ercc5tm2a(EUCOMM)Hmgu/BcmMmucd. The experiment will tell us which loci genome-wide 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.