Epigenetic regulation of V(D)J recombination

Chromosome breaks are dangerous business, carrying the risk of loss of genetic information or, even worse, misrepair of the break, leading to outcomes such as dicentric chromosomes or oncogenic translocations Yet V(D)J recombination, a process that breaks, rearranges and repairs chromosomes, is crucial to the development of the adaptive immune system, for it gives Band T-cells the capacity to generate a virtually unlimited repertoire of antigen receptor proteins to combat an equally vast array of antigens To minimize the risks inherent in chromosomal breakage, V(D)J recombination is carefully orchestrated at multiple levels, ranging from DNA sequence requirements all the way up to chromatin conformation and nuclear architecture In the present chapter we introduce various regulatory controls, with an emphasis on epigenetic mechanisms and recent work that has begun to elucidate their interdependence