No abstract

SUMMARY In this study, we describe the 3D regulatory chromosome structural landscape of human naive and primed embryonic stem cells. To devise this map, we identified transcriptional enhancers and insulators in these cells and placed them within the context of cohesin-associated CTCF-CTCF loops using cohesin ChIA-PET data. The CTCF-CTCF loops we identified form a chromosomal framework of insulated neighborhoods, which in turn form topologically associated domains (TADs), that are largely preserved during transition between the naïve and primed states. Regulatory changes in enhancer-promoter interactions occur within insulated neighborhoods during cell state transition. The CTCF anchor regions we identified are conserved across species, influence gene expression, and are a frequent site of mutations in cancer cells, underscoring their functional importance in cellular regulation. These 3D regulatory maps of human pluripotent cells therefore provide a foundation for future interrogation of the relationships between chromosome structure and gene control in development and disease.

Highlights d Genome organization is highly variable between individual cells d Physical interaction between any two genome regions is a relatively rare event d The structure of TADs is malleable and variable between individual cells d The interactions of two alleles in the same nucleus are independent of each other