Extended Data Fig. 7: Interactions of IGCR1 or Cer-Sis with VH or Vκ locus in v-Abl cells. Related to Fig. 4 and Extended Data Fig. 3.
From: Molecular basis for differential Igk versus Igh V(D)J joining mechanisms
a, Upper panel: 3C-HTGTS profiles in the Vκ locus from single Jκ5-single Igh v-Abl line baiting from Cer CBE1. Lower panel: 3C-HTGTS profiles in the Vκ locus from Igh-Igκ hybrid-Vκ v-Abl line baiting from IGCR1 CBE1. b, 3C-HTGTS profiles in the VH locus from single Jκ5-single Igh line baiting from IGCR1 CBE1. CBE sites are shown in a and b with orientations labeled as in Extended Data Fig. 3a. 3C-HTGTS data are presented as mean ± s.e.m. from 3 biological repeats (a) or as mean value from 2 biological repeats (b). c, Schematic loop ___domain illustrations of Igκ, Igh, and Igh-Igκ hybrid-Vκ loci based on 3C-HTGTS data shown in a and b. (i) In Igκ locus, the strong anchoring activity of Cer-Sis, coupled with relatively weak impediments in the Vκ locus, allows loop extrusion anchored at Cer to extend across the distal, middle and proximal Vκ domains, as shown in a, upper panel. (ii) In Igh-Igκ hybrid-Vκ locus, loop extrusion anchored at IGCR1 can extend a considerable distance into proximal and middle Vκ domains with weak Vκ locus impediments, but does not extend as far as that in (i), because IGCR1 is a less stable anchor than Cer-Sis and more likely to be disassembled before loop extrusion has a chance to proceed into the distal Vκ locus, as shown in a, lower panel. (iii) In Igh locus without WAPL down-regulation, strong VH locus impediments only allow loop extrusion to bring the most proximal VH region to IGCR1, while upstream interactions are completely blocked by the “wall” of proximal VH CBEs, as shown in b. Elements and proteins illustrated are indicated in the box.
