Control of Cell Identity Genes Occurs in Insulated Neighborhoods in Mammalian Chromosomes

The pluripotent state of embryonic stem cells (ESCs) is produced by active transcription of genes that control cell identity and repression of genes encoding lineage-specifying developmental regulators. Here, we use ESC cohesin ChIA-PET data to identify the local chromosomal structures at both active and repressed genes across the genome. The results produce a map of enhancer-promoter interactions and reveal that super-enhancer-driven genes generally occur within chromosome structures that are formed by the looping of two interacting CTCF sites co-occupied by cohesin. These looped structures form insulated neighborhoods whose integrity is important for proper expression of local genes. We also find that repressed genes encoding lineage-specifying developmental regulators occur within insulated neighborhoods. These results provide insights into the relationship between transcriptional control of cell identity genes and control of local chromosome structure. [Display omitted] •Cohesin ChIA-PET reveals local chromosome structures in the ES cell genome•Super-enhancer-driven cell identity genes occur in insulated chromosome loops•Polycomb-bound lineage-specifying genes occur in insulated chromosome loops•Integrity of insulated neighborhoods is important for normal gene expression In embryonic stem cells, both super-enhancer-driven cell identity genes and repressed lineage-specifying genes occur in insulated neighborhoods. The integrity of these structural neighborhoods is important for proper expression of nearby genes.