GSE133126
Widespread reorganisation of pluripotent factor binding and gene regulatory interactions between human pluripotent states
The transition from naive to primed pluripotency is accompanied by an extensive reorganisation of transcriptional and epigenetic programmes. However, the role of transcriptional enhancers and three-dimensional chromatin organisation in coordinating these developmental programmes remains incompletely understood. Here, we generated a high-resolution atlas of gene regulatory interactions, chromatin profiles and transcription factor occupancy in naive and primed human pluripotent stem cells, and developed a network-graph approach to examine the atlas at multiple spatial scales. We uncovered highly connected promoter hubs that changed substantially in interaction frequency and in transcriptional co-regulation between pluripotent states. Small hubs frequently merged to form larger networks in primed cells, often linked by newly-formed Polycomb-associated interactions. We identified widespread state-specific differences in enhancer activity and interactivity that corresponded with an extensive reconfiguration of OCT4, SOX2 and NANOG binding and target gene expression. These findings provide new, multilayered insights into the chromatin-based gene regulatory control of human pluripotent states. Overall design: We generated Hi-C (one replicate) and PCHi-C (two replicates) data sets for naïve and primed human pluripotent stem cells (hPSCs). We also generated ChIP-seq data sets in naïve hPSCs including NANOG (two replicates), SOX2 (two replicates) and input (two replicates). We also generated CUT&RUN datasets for H3K4me1 in naive (two replicates) and primed hPSCs (three replicates).