Sequential enhancer sequestration dysregulates recombination center formation at the IgH locus
Here we report that in the absence of intergenic control region 1 (IGCR1) the intronic enhancer (Eµ) associates with the next available CTCF binding site located close to VH81X, via putative heterotypic interactions involving YY1 and CTCF. Figure 1 and S3 show that Eµ loops to an alternate site close to the 3’-most functional VH gene segment, VH81X, upon disruption of its interaction with IGCR1. Figure 2 and S4 support that Eu-VH81X loop requires both YY1 and CTCF. Figure 3 and S5 demonstrate that DFL16.1 utilization is reduced on IGCR1-deficient alleles. Figure 4 and S6 shown that VH (VH713 and VHQ52) recombination is greatly induced and Eu-dependent on IGCR1-deficient alleles. Figure S7 show the verification of IGCR1 deleted cell line. Figure 6 and S8 support that distal VH is replaced from recombination center. Figure S10A show the versification of proximal VH deletion. Figure S10B provide information for recombination in different cell lines.