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 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.
Department of Microbiology and Immunology, Vanderbilt University, Nashville, TN 37232, USA.
Michael L
ML
Sikes
Amber
A
Meade
Rajkamal
R
Tripathi
Michael S
MS
Krangel
Eugene M
EM
Oltz
D000107:Acetylation; D002460:Cell Line; D004254:DNA Nucleotidyltransferases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005803:Genes, Immunoglobulin; D016654:Genes, RAG-1; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008957:Models, Genetic; D009687:Nuclear Proteins; D011401:Promoter Regions, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011995:Recombination, Genetic; D014162:Transfection; D045567:VDJ Recombinases
D004268:DNA-Binding Proteins; D006657:Histones; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004254:DNA Nucleotidyltransferases; D045567:VDJ Recombinases