Compartmentalization of the TAL1 regulon via looping interactions between CTCF/RAD21-bound elements. (A) Schematic organization of CTCF elements at the human TAL1 locus. Locations and directions of transcription of TAL1 and its flanking genes PDZK1IP1, STIL, and CMPK1 are shown by the horizontal gray arrows. Locations of promoters and enhancers are shown with vertical gray arrows. CTCF/RAD21-occupied elements studied here (+57, +53, +40, and −31) are highlighted (vertical black arrows). Scale (in kb) is shown. Looping interactions tested in this study are denoted by dotted gray lines with arrowheads. (B) Bar diagrams of looping interactions between CTCF/RAD21-bound elements determined by 3C in human erythroid (K562) and lymphoid (HPB-ALL) cell lines. (C) Comparison of interaction patterns between CTCF/RAD21-bound elements at the TAL1 locus in human K562 and HPB-ALL cells normalized against ERCC3 ligation frequencies. (D) Schematic diagram depicted the hypothesized proximity (gray dotted arrowhead) between the TAL1 promoters (PTAL1) and the −31 element based on the data described in the text, shown here, and in Figures 1 and 3. CTCF (light gray sphere) and RAD21 (dark gray sphere) occupancies are depicted. (E) Bar diagram of looping interactions, measured as relative ligation frequencies (black bars), between the −31 element and TAL1 promoter 1b (PTAL1) in K562 and HPB-ALL cell lines. (F) Comparison of interaction patterns between the TAL1 promoters and the −31 insulator element in human K562 and HPB-ALL cells normalized against ERCC3 ligation frequencies. Color coding of the cell lines is the same as in panel C. For the bar diagrams in panels B and E, interactions, measured at relative ligation frequencies (black bars), are shown with SEs. Locations of 3C “bait” regions are denoted by vertical gray arrows. P values are indicated for relative ligation frequencies which are significantly higher for test regions when compared with those of control regions. (B,E) Scales (in kb) are shown at the bottom of panels. (C,F) P values are indicated for interactions which are significantly higher in K562 (TAL1 expressing). **P < .01; ****P < .0001.