Antisense intergenic transcription in V(D)J recombination.
Antigen receptor genes undergo variable, diversity and joining (V(D)J) recombination, which requires ordered large-scale chromatin remodeling. Here we show that antisense transcription, both genic and intergenic, occurs extensively in the V region of the immunoglobulin heavy chain locus. RNA fluorescence in situ hybridization demonstrates antisense transcription is strictly developmentally regulated and is initiated during the transition from DJ(H) to VDJ(H) recombination and terminates concomitantly with VDJ(H) recombination. Our data show antisense transcription is specific to the V region and suggest transcripts extend across several genes. We propose that antisense transcription remodels the V region to facilitate V(H)-to-DJ(H) recombination. These findings have wider implications for V(D)J recombination of other antigen receptor loci and developmental regulation of multigene loci.
Bolland
Daniel J
DJ
Laboratory of Chromatin and Gene Expression, The Babraham Institute, Cambridge CB2 4AT, UK.
Wood
Andrew L
AL
Johnston
Colette M
CM
Bunting
Sam F
SF
Morgan
Geoff
G
Chakalova
Lyubomira
L
Fraser
Peter J
PJ
Corcoran
Anne E
AE
D000818:Animals; D016373:DNA, Antisense / Q000378:metabolism*; D021901:DNA, Intergenic / Q000378:metabolism*; D015321:Gene Rearrangement / Q000502:physiology*; D005803:Genes, Immunoglobulin / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D008810:Mice, Inbred C57BL; D012313:RNA / Q000378:metabolism; D014158:Transcription, Genetic / Q000502:physiology*
D016373:DNA, Antisense; D021901:DNA, Intergenic; D018398:Homeodomain Proteins; C064658:RAG-1 protein; D012313:RNA