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At steady state, the V region is in proximity to allIGHenhancers forming theIGHhub. The hub is stabilized through dynamic, multivalent interactions between low-complexity domains found in various transcriptional proteins. Transcriptional activation and mutation occur via the diffusion of factors between enhancers and genes. Ectopic transcription ofIGHG1results in the recruitment of this gene into the hub independently of loop extrusion. Within the hub,IGHG1comes under the influence of the 3′RRs resulting in AID recruitment and mutagenesis of its Sγ1 S region. However, V region transcription and SHM are unaffected under these conditions implying that the 3′RRs retain their relative proximity to, and activity toward, the V region. The inference is that SHM and CSR may be compatible rather than competitive.

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