The 3D architecture of the genome determines specificity of HNF1β-mediated gene regulation (ATAC-Seq)

Similar to other studies, promoter connectivity correlated with gene expression levels of the participating genes. As proof of principle, we studied the importance of long-range chromatin interactions in transcriptional regulation mediated by transcription factor HNF1β. Our analysis revealed that HNF1β controls the expression of housekeeping genes primarily by binding to promoters in close proximity of the transcription start site (TSS) of the gene, while the expression of developmental genes is regulated by both promoters and distal enhancers.

Moreover, by employing a CRISPR/Cas9 enhancer mutant, we demonstrated that Caveolin-1 expression is regulated by an HNF1β-bound enhancer ~95kb from the TSS of the gene. In conclusion, we describe the first Hi-C map in a DCT cell line and demonstrate that the 3D architecture of the genome controls specificity of HNF1β-mediated gene transcription.