Extended Data Fig. 7: CBEs inserted upstream of Iα lead to increased inversional Sα CSR.

a, Three repeats of RAD21 ChIP–seq profiles of CD40–IL-4–TGFβ-stimulated i3CBEs AID^−/− cells. b, c, Additional repeats of the 3C-HTGTS profiles shown in Fig. 3f, g, from CD40–IL-4–TGFβ-stimulated CH12F3NCΔ AID^−/− and i3CBEs AID^−/− cells using CBE insertion (b) or iEμ–Iμ (c) locale as baits (blue asterisks). b, Right, 3C-HTGTS profiling shows the digestion and bait strategies used. d, Model to address increased inversional Sα CSR in CH12F3 cells with CBEs inserted upstream of Iα. I, Cohesin is loaded at various Igh locations including transcriptionally activated Iα–Sα. II–VII, For cohesin loaded at the Iα locale, extrusion past the CBE impediment allows a significant subset of cells to reach step VII to generate CSRC. VIII–X, In these cells, a significant portion of continued upstream extrusion passes by the CBE impediment to yield cells in the population with configurations shown in steps IX and X. XI–XIV, The cells with the configuration shown in IX will have both deletional (XIII) and inversional (XIV) joining mediated by a diffusion-related process in the absence of complete Sμ–Sα synapsis (see main text for more details). Those with the configuration shown in X will join via deletion as described in Extended Data Fig. 5e. This working model could be explained by other variations as indicated for other model figures.