Pre-B Cell Receptor Signaling Induces Immunoglobulin κ Locus Accessibility by Functional Redistribution of Enhancer-Mediated Chromatin Interactions
Figure 5
Long-range chromatin interactions of κ regulatory elements correlate with Vκ gene usage.
(A) Selected examples of genomic regions containing Vκ+ fragments, showing increased (Vκ4–57, Vκ6–25, Vκ8–24, Vκ4–79), stable (Vκ8–23–1, Vκ4–78, Vκ13–84), or decreased (Vκ3–9, Vκ14–111) 3C-seq interaction frequencies with 3′Eκ or iEκ upon pre-BCR signaling. Averaged 3C-seq signals are plotted as a line graph, with the individual data points representing the center of the BglII restriction fragments. Yellow shading marks the BglII fragment on which the Vκ gene(s) is located. Vκ gene(s) are indicated (top) and chromosomal coordinates and scale bars (10 kb) are plotted (bottom). (B) Classification of Vκ+ fragments, based on the effect of pre-BCR signaling on their interactions with the three κ regulatory elements indicated. Increase and decrease were defined as >1.5-fold change of interaction frequencies detected in WT pre-B cells versus Btk−/−Slp65−/− pre-B cells. (C) Correlation of average interaction frequencies (for the three κ regulatory elements indicated) with four Vκ usage categories ranging from low (<0.1%) to high usage (>0.5%, listed in the table on the right). Diamonds represent average interaction frequencies for Btk−/−Slp65−/− pre-B cells (yellow) and WT pre-B cells (grey). The dotted line in each graph depicts the average interaction frequency with fragments that do not contain a functional Vκ (Vκ−). Primary Vκ gene usage data were taken from [54].