An inter-dependent network of enhancers regulates INK4a/ARF locus

By functionally dissecting densest enhancer cluster in the gene desert at 9P21 locus, we identified a non-redundant inter-dependent enhancer network that functions over long distances, the perturbation in any enhancer in the network results in the complete collapse of entire enhancer cluster and target genes activity. The enhancer network can be targeted to regulate INK4a/ARF locus in associated pathophysiologies and cancers. Overall design: The inter-dependent enhancer network was identified by series of deletions of enhancers that interacted with CDKN2A promoters.The RNA-seq upon these deletions displays the GO terms that are directly related to Coronary artery disease and Typ2-diabetes.