Intrachromosomal interactions across the intestinal crypt-villus axis and the imapct on chromatin looping upon HNF4 loss

This study provides a map of enhancer-promoter interactions in the intestinal epithelium. We find that key drivers of intestinal differentiation, HNF4 transcription factors, are required for enhancer-promoter interactions at their direct target genes. Depletion of HNF4 disrupts chromatin looping, nearby enhancer chromatin, and target gene expression. H3K4me3 HiChIP-seq, ATAC-seq and MNase ChIP-seq of active chromatin markers (H3K4me2 and H3K27ac) were employed to survey enhancer-promoter interactions in crypt and villus cells of the intestinal epithelium. By comparing H3K4me3 HiChIP-seq profiles of Hnf4DKO and their littermate controls, HNF4-dependent enhancer-promoter interactions in the mouse duodenal epithelium were also identified in this study.