Three-dimensional architecture of the IgH locus facilitates class switch recombination

Immunoglobulin (Ig) class switch recombination (CSR) is responsible for diversification of antibody effector function during an immune response. This region-specific recombination event, between repetitive switch (S) DNA elements, is unique to B lymphocytes and is induced by activationinduced deaminase (AID). CSR is critically dependent on transcription of noncoding RNAs across S regions. However, mechanistic insight regarding this process has remained unclear. New studies indicate that long-range intrachromosomal interactions among IgH transcriptional elements organize the formation of the S/S synaptosome, as a prerequisite for CSR. This three-dimensional chromatin architecture simultaneously brings promoters and enhancers into close proximity to facilitate transcription. Here, we recount how transcription across S DNA promotes accumulation of RNA polymerase II, leading to the introduction of activating chromatin modifications and hyperaccessible chromatin that is amenable to AID activity.