Promoters are central players in regulating expression levels of genes. However, it is through their interactions with distal acting enhancers, that they achieve specific patterns of expression in different cells, tissues and developmental stages. In general, regulatory mutations carry lower burdens for the fitness of individuals than those of protein-coding mutations. Indeed, most of the variants associated with complex diseases are non-coding, and a large fraction of them (77%) are located within enhancers (Maurano MT et al, 2012). Therefore, it is of paramount importance to locate their target genes to discover their functional contribution to disease.
We developed Capture Hi-C (HiCap) by combining Hi-C (4-cutter) and sequence capture methodologies to only capture interactions of regions of interest such as promoters (Sahlén P et al 2015). Recently, we applied Capture Hi-C in vascular and skin inflammatory disease context and discovered novel genes and processes potentially contributing to disease onset and progress through mapping risk variants to their target genes in relevant tissues.
Currently our group is developing novel methodologies for the detection of promoter-enhancer interactions at the single cell level. We investigate the role of rare enhancer variants in human disease context. Moreover, we are mapping promoter-enhancer interactions in various dog and wolf tissues to establish the contribution of functional non-coding to domestication and adaptation of the dog from its wolf ancestors.
Jörg Bachmann, post-doc
Hassan Bassereh, post-doc
Artemy Zhigulev, PhD student
Robert William Baber, PhD student
Sailendra Pradhananga, PhD student