Regulation of V(D)J recombination: A dominant role for promoter positioning in gene segment accessbility

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 inProceedings of the National Academy of Sciences - PNAS Vol. 99; no. 19; p. 12309
Main Authors Sikes, Michael L, Meade, Amber, Tripathi, Rajkamal, Krangel, Michael S, Oltz, Eugene M
Format Journal Article
LanguageEnglish
Published Washington National Academy of Sciences 17.09.2002
Subjects
Genes
Immunology
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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 beta 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