Regulation of antigen receptor gene assembly by genetic–epigenetic crosstalk

Many aspects of gene function are coordinated by changes in the epigenome, which include dynamic revisions of chromatin modifications, genome packaging, subnuclear localization, and chromosome conformation. All of these mechanisms are used by developing lymphocytes to regulate the assembly of functional antigen receptor genes by V(D)J recombination. This somatic rearrangement of the genome must be tightly regulated to ensure proper B and T cell development and to avoid chromosomal translocations that cause lymphoid tumors. V(D)J recombination is controlled by a complex interplay between cis-acting regulatory elements that use transcription factors as liaisons to communicate with epigenetic pathways. Genetic–epigenetic crosstalk is a key strategy employed by precursor lymphocytes to modulate chromatin configurations at Ig and Tcr loci and thereby permit or deny access to a single V(D)J recombinase complex. This article describes our current knowledge of how genetic elements orchestrate crosstalk with epigenetic mechanisms to regulate recombinase accessibility via localized, regional, or long-range changes in chromatin.