Epigenetic regulation of antigen receptor rearrangement.

In the mammalian immune system, V(D)J rearrangement of immunoglobulin (Ig) and T-cell receptor (TCR) genes is regulated in a lineage- and stage-specific fashion. Because each of the seven loci capable of rearrangement utilizes the same recombination machinery, it is thought that V(D)J recombination of each antigen receptor locus is regulated through the differential accessibility of each locus to the V(D)J recombination machinery. Accumulating evidence indicates that chromatin remodeling mediated by DNA methylation and demethylation plays important roles in regulating V(D)J recombination and germline transcription through the Ig and TCR loci. DNA demethylation within the antigen receptor loci appears to be regulated by cis-elements also required for coordinated V(D)J recombination and germline transcription. In this paper, we critically examine the relationship between demethylation and V(D)J recombination as well as the mechanism to regulate DNA demethylation within the antigen receptor loci.