Figure 6. cPRC1 loops prime subsequent active CTCF loops during differentiation.

a, Virtual 4C analysis of Foxf2/Foxc1 locus using Hi-C data in WT and Pcgf2^−/− ESCs and NPCs. The bait was set at the loop anchor at Foxf2 (highlighted in red). Note the increased interactions in NPCs outside of the loop domain (highlighted in green) and the decreased interaction between Foxf2 and Foxc1 (highlighted in purple) in the WT cells. Interactions are normalized based on the peak height of the bait. b, HiChIP analysis for H3K4me3, from a previous study⁴⁶, shows the increase of promoter-enhancer or promoter-promoter loops in WT NPCs compared with ESCs (top panel). These loops are weakened when Ctcf is deleted (bottom panel). These loops are well correlated with the Virtual 4C peaks. c, ChIP-seq tracks showing the enrichment for Pcgf2, Ring1B, Ctcf, H3K4me3, and H3K27ac in WT ESCs and NPCs. d, APA plots for cPRC1.2 loops targeting neuro-ectoderm genes (top) or non-neuro-endoderm genes (bottom) in WT ESCs and NPCs at 10-kb resolution. Normalized pileup values are displayed at the top-left. e, Schematic model illustrating the role of cPRC1.2 loops in regulating lineage-specific gene expression through establishing a primed state for subsequent CTCF-mediated loops during neuronal differentiation.