Looping organization of TAL1 regulatory hubs. (A) Schematic organization of the human TAL1 locus and looping interactions between its regulatory elements identified in this study across all cell types. The scale (in kb) is shown to the right. Exon-intron structures (joined-up black bars) of TAL1 and its flanking genes PDZK1IP1, STIL, and CMPK1 and directions of transcription (gray arrows) are shown at the top of the panel. Promoters, enhancers, and CTCF binding sites are the vertical black arrows; the Jurkat −7 enhancer and −81/TAL^d are also shown. Interactions between TAL1 promoter 1b and its enhancers, between enhancers, and between CTCF/RAD21-bound elements are shown with black loops. (B) Schematic models of looping hubs at the TAL1 locus in 3 different cell types: (i) TAL1-expressing erythroid cells (K562) (assuming the −10 enhancer is also present in the active hub), (ii) TAL1-expressing lymphoid T-ALL cells (Jurkat) (assuming loops detected in this study are occurring in the same nuclei), and (iii) TAL1-nonexpressing lymphoid T-ALL cells (HPB-ALL) (assuming loops detected in this study are occurring in the same nuclei). Locations of promoters, enhancers, and CTCF/RAD21-bound elements are depicted as in the preceding figures. Direction of transcription of relevant genes (gray arrows) and Pol II machinery (dark gray lobules) are also shown and detailed in the key. Unknown factors mediating the interaction of the stem cell enhancer, the TAL1 promoters, and the −31 element in HPB-ALL are represented by the light gray ball. The looping interactions of CTCF/RAD21-bound elements in Jurkat cells were not studied here; thus, the location of the −31 element in the TAL1-expressing hub in Jurkat cells is not known and is denoted by a question mark (?). In all 3 models, contacts between TAL^d (and P^STIL located ∼1 kb away) and the TAL1 hubs are shown. Note: Interaction frequencies between TAL1 cis-regulatory elements in HPB-ALL were overall at lower levels than in either K562 or Jurkat, as depicted in the models.