AID targeting is dependent on RNA polymerase II pausing

Activation induced deaminase (AID) is globally targeted to immunoglobulin loci, preferentially focused to switch (S) regions and variable (V) regions, and prone to attack hotspot motifs. Nevertheless, AID deamination is not exclusive to Ig loci and the rules regulating AID targeting remain unclear. Transcription is critically required for class switch recombination and somatic hypermutation. Here, I consider the unique features associated with S region transcription leading to RNA polymerase II pausing, that in turn promote the introduction of activating chromatin remodeling, histone modifications and recruitment of AID to targeted S regions. These findings allow for a better understanding of the interplay between transcription, AID targeting and mistargeting to Ig and non-Ig loci.

► AID targeting to Ig loci occurs via an integrated transcriptional mechanism.
► Germline transcript expression generates chromatin accessibility.
► Elongating RNA polymerase II is paused along the length of S regions.
► RNA polymerase II pausing is dependent on S region R-loops.
► RNA polymerase II pausing factors recruit AID to S regions.