A role for histone acetylation in the developmental regulation of VDJ recombination.
VDJ 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 VDJ recombination reporter and the endogenous T cell receptor alpha/delta locus. Enhancer activity was shown to impart long-range, developmentally regulated changes in H3 acetylation, and H3 acetylation status was tightly linked to VDJ recombination. H3 hyperacetylation is proposed as a molecular mechanism coupling enhancer activity to accessibility for VDJ recombination.
McMurry
M T
MT
Department of Immunology, Post Office Box 3010, Duke University Medical Center, Durham NC 27710, USA.
Krangel
M S
MS
D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D004254:DNA Nucleotidyltransferases / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015329:Gene Rearrangement, T-Lymphocyte; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D019676:Genes, T-Cell Receptor delta; D006657:Histones / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000378:metabolism*; D019076:Transgenes; D045567:VDJ Recombinases
D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; D021382:Protein Sorting Signals; C499311:RAG2 protein, human; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases