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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Cell Line
  • Chromatin / metabolism
  • Epigenesis, Genetic*
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain*
  • Genes, Immunoglobulin Heavy Chain*
  • Histones / metabolism
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Joining Region / genetics*
  • Immunoglobulin Variable Region / genetics*
  • Mice
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / metabolism
  • Recombinases / metabolism
  • Recombination, Genetic


  • Chromatin
  • Histones
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Joining Region
  • Immunoglobulin Variable Region
  • Recombinases