Genomic dissection of enhancers uncovers principles of combinatorial regulation and cell type-specific wiring of enhancer-promoter contacts.

ABSTRACT: Genomic binding of transcription factors, like the glucocorticoid receptor (GR), is linked to the regulation of genes. However, as we show here, GR binding is a poor predictor of GR-dependent gene regulation even when taking the 3D organization of the genome into account. To connect GR binding sites to the regulation of genes in the endogenous genomic context, we turned to genome editing. By deleting GR binding sites, individually or in combination, we uncovered how cooperative interactions between binding sites contribute to the regulation of genes. Specifically, for the GR target gene GILZ, we show that the simultaneous presence of a cluster of GR binding sites is required for the activity of an individual enhancer and that the GR-dependent regulation of GILZ depends on multiple GR-bound

SUBMITTER: Thormann V 

PROVIDER: S-EPMC5888794 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature