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Regulation of V(D)J recombination: a dominant role for promoter positioning in gene segment accessibility.

Sikes ML, Meade A, Tripathi R, Krangel MS, Oltz EM.

Department of Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.

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.

Publication Types:
PMID: 12196630 [PubMed - indexed for MEDLINE]

PMCID: PMC129441