Localized epigenetic changes induced by D H recombination restricts recombinase to DJ H junctions

Ramesh Subrahmanyam, Hansen Du, Irina Ivanova, Tirtha Chakraborty, Yanhong Ji, Yu Zhang, Frederick W. Alt, David G. Schatz, Ranjan Sen

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1205-1212
Number of pages8
JournalNature Immunology
Volume13
Issue number12
DOIs
StatePublished - Dec 2012
Externally publishedYes

ASJC Scopus subject areas

  • Immunology

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