A Role for Histone Acetylation in the Developmental Regulation of V(D)J Recombination

Abstract

V(D)J recombination is developmentally regulated in vivo by enhancer-dependent changes in the accessibility of chromosomal recombination signal sequences to the recombinase, but the molecular nature of these changes is unknown. Here histone H3 acetylation was measured along versions of a transgenic V(D)J recombination reporter and the endogenous T cell receptor α/δ locus. Enhancer activity was shown to impart long-range, developmentally regulated changes in H3 acetylation, and H3 acetylation status was tightly linked to V(D)J recombination. H3 hyperacetylation is proposed as a molecular mechanism coupling enhancer activity to accessibility for V(D)J recombination.