Panel A: Trace line graphs showing Cut and Run-sequencing peak profiles for genes involved in the germinal center response, including Cd83, Pim1, Bcl6, and Pax5. The x-axis represents genomic coordinates, and the y-axis represents signal intensity. The graphs compare wild-type (WT) and AID R112H mutant profiles. Panel B: Trace line graphs showing Cut and Run-sequencing peak profiles for genes involved in plasma cell differentiation, including Irf4, Xbp1, and Prdm1. The x-axis represents genomic coordinates, and the y-axis represents signal intensity. The graphs compare wild-type (WT) and AID R112H mutant profiles. Panel C: Structural analysis of Irf4 probe binding to AID active-site cleft. The upper part shows the binding to WT and R112H AID protein. The left lower part shows zoomed views of the simulated docked complex with the AGCT motif displayed. The bottom lists the values for the top-ranked structures, including HADDOCK score, RMSD value, Van der Waals energy, and Electrostatic energy.
Association of AID, TET2, and histone mark H3K4me3 with AID off-target genes. (A) CUT&RUN-sequencing peak profiles of genes involved in the GC response including Cd83, Pim1, Bcl6, and Pax5.(B) CUT&RUN-sequencing peak profiles for genes involved in PC differentiation including Irf4, Xbp1, and Prdm1. The enrichment profiles represent the mean of two separate experiments sequenced at the same time. (C)Irf4 probe binding to AID active-site cleft. Left upper: Irf4 probe binding to WT and R112H AID protein. Left lower: Zoomed views of the simulated docked complex. The AGCT motif is displayed as licorice representation, and cytosine is colored in green (carbon atoms). Right: The values for the top-ranked structures. The values were obtained from HADDOCK software. a, HADDOCK score. b, RMSD (Å) value from the overall lowest-energy structure. c, van der Waals energy (kcal/mol). d, electrostatic energy (kcal/mol).