Regulation of V(D)J Recombination: A Dominant Role for Promoter Positioning in Gene Segment Accessibility

Antigen receptor gene assembly is regulated by transcriptional promoters and enhancers, which control the accessibility of gene segments to a lymphocyte-specific V(D)J recombinase. However, it remained unclear whether accessibility depends on the process of transcription itself or chromatin modifica...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2002-09, Vol.99 (19), p.12309-12314
Main Authors: Sikes, Michael L., Meade, Amber, Tripathi, Rajkamal, Krangel, Michael S., Oltz, Eugene M.
Format: Article
Language:English
Subjects:
Acetylation
Biological Sciences
Cell Line
Chromatin
DNA
DNA Nucleotidyltransferases - genetics
DNA Nucleotidyltransferases - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Enzymes
Genes
Genes, Immunoglobulin
Genes, RAG-1
Genetic loci
Genomics
Histones
Histones - chemistry
Histones - metabolism
Homeodomain Proteins - genetics
Homeodomain Proteins - metabolism
Humans
Lymphocytes - immunology
Lymphocytes - metabolism
Models, Genetic
Nuclear Proteins
Polymerase chain reaction
Promoter Regions, Genetic
Receptors, Antigen, T-Cell, alpha-beta - genetics
Recombination, Genetic
Transcriptional regulatory elements
Transfection
VDJ Recombinases
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Summary:Antigen receptor gene assembly is regulated by transcriptional promoters and enhancers, which control the accessibility of gene segments to a lymphocyte-specific V(D)J recombinase. However, it remained unclear whether accessibility depends on the process of transcription itself or chromatin modifications that accompany transcription. By using T cell receptor β substrates that integrate stably into nuclear chromatin, we show that promoter location, rather than germ-line transcription or histone acetylation, is a primary determinant of recombination efficiency. These spatial constraints on promoter positioning may reflect an RNA polymerase-independent mechanism to target adjacent gene segments for chromatin remodeling events that facilitate rearrangement.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.182166699