Functional importance of dynamic CTCF-binding sites. (A) Heatmap showing the unsupervised hierarchical clustering based on Pearson correlation of ATAC-seq signals on dynamic CTCF peaks across different blood lineages. The hierarchical cluster was generated based on the Pearson correlation of normalized ATAC-seq signals within dynamic CTCF sites. The chromatin accessibility within dynamic CTCF sites in each blood cell types were calculated based on ATAC-seq data generated in the previous publication.¹⁹  (B) Functional annotation results of dynamic CTCF sites for the top Gene Ontology cellular component and phenotype from GREAT. The radius of the circle represents the significance, −log10(FDR), of the enrichment. (C) Enrichment significance of trait-associated SNPs within different types of dynamic CTCF-binding sites. (D) Schematic of the pooled sgRNA library design and screening procedure used to experimentally validate the function of dynamic CTCF-binding sites. (E) Pie chart showing the numbers of dynamic CTCF-binding sites with different functions based on sgRNA perturbation results. CLP, common lymphoid progenitor; CMP, common myeloid progenitor; GMP, granulocyte-monocyte progenitor; HSC, hematopoietic stem cell; LMPP, lymphomyeloid primed progenitor; MEP, megakaryocytic-erythroid progenitor; MPP, myeloid primed progenitor; NK, natural killer.