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Nat Immunol. 2012 Dec;13(12):1205-12. doi: 10.1038/ni.2447. Epub 2012 Oct 28.

Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions.

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1
Laboratory of Molecular Biology and Immunology, National Institute on Aging, US National Institutes of Health, Baltimore, Maryland, USA.

Abstract

Genes encoding immunoglobulin heavy chains (Igh) are assembled by rearrangement of variable (V(H)), diversity (D(H)) and joining (J(H)) gene segments. Three critical constraints govern V(H) recombination. These include timing (V(H) recombination follows D(H) recombination), precision (V(H) gene segments recombine only to DJ(H) junctions) and allele specificity (V(H) recombination is restricted to DJ(H)-recombined alleles). Here we provide a model for these universal features of V(H) recombination. Analyses of DJ(H)-recombined alleles showed that DJ(H) junctions were selectively epigenetically marked, became nuclease sensitive and bound RAG recombinase proteins, which thereby permitted D(H)-associated recombination signal sequences to initiate the second step of Igh gene assembly. We propose that V(H) recombination is precise, because these changes did not extend to germline D(H) segments located 5' of the DJ(H) junction.

PMID:
23104096
PMCID:
PMC3685187
DOI:
10.1038/ni.2447
[Indexed for MEDLINE]
Free PMC Article
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