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

Michael L. Sikes, Amber Meade, Rajkamal Tripathi, Michael S. Krangel, Eugene M. Oltz

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)12309-12314
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number19
DOIs
StatePublished - Sep 17 2002

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