Non-coding transcription and large-scale nuclear organisation of immunoglobulin recombination

The enormous antigen receptor loci in lymphocytes are a paradigm of dynamic nuclear organisation, which is integral to their need to move extensively in 3D space to achieve distal gene synapse for V(D)J recombination and allelic exclusion. The loci undergo extensive 3D looping to bring distal genes together, controlled by several tissue-specific and ubiquitous factors, but how these factors achieve looping, synapsis and V(D)J recombination has been a mystery. Now several studies provide evidence that non-coding transcription, often proposed to play a role, is indeed an important driver, and furthermore has a specific nuclear destination for recombination. Both local transcription-independent looping and longer range factor-mediated transcription-dependent looping play separate roles in altering AgR architecture to enable V(D)J recombination.