Epigenetic regulation of antigen receptor gene rearrangement

Recent studies of the regulation of antigen receptor rearrangement have revealed several completely new levels of control. Not only do antigen receptor loci undergo changes in histone modifications as they become accessible for recombination, but also the number of different histone modifications and the variation at different parts of each receptor locus reveal great complexity. RAG2 is now known to bind to one of these histone modifications, H3K4me3, and this targets the initial RAG binding events to the J genes. The large megabase receptor loci undergo 3D changes in their structure during rearrangement, and receptor loci move throughout the nucleus, transiently binding to heterochromatin, and transiently pairing with each other. RAG-mediated DNA breaks promote some of these movements, and also result in widespread changes in the transcriptional profile promoting differentiation.