Regulation of T cell receptor-alpha gene recombination by transcription.
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Regulation of T cell receptor-alpha gene recombination by transcription. / Abarrategui, Iratxe; Krangel, Michael S.
I: Nature Immunology, Bind 7, Nr. 10, 2006, s. 1109-15.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Regulation of T cell receptor-alpha gene recombination by transcription.
AU - Abarrategui, Iratxe
AU - Krangel, Michael S
N1 - Keywords: Animals; Chromatin Assembly and Disassembly; Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; Genes, T-Cell Receptor alpha; Immunoglobulin Joining Region; Mice; Mice, Mutant Strains; Promoter Regions (Genetics); Recombination, Genetic; Sequence Deletion; Transcription, Genetic
PY - 2006
Y1 - 2006
N2 - Despite the longstanding correlation between transcription and variable-(diversity)-joining (V(D)J) recombination, it is unknown whether transcription itself can direct recombinase targeting. Here we show that blockade of transcriptional elongation through the mouse T cell receptor-alpha (Tcra) locus suppressed V(alpha)-to-J(alpha) recombination and chromatin remodeling of J(alpha) segments. Transcriptional blockade also derepressed cryptic J(alpha) promoters. Our results demonstrate two key functions for transcription in Tcra locus regulation. Transcription increases the recombination of J(alpha) segments located within several kilobases of a promoter and prevents the activation of downstream promoters through transcriptional interference. These influences promote an ordered progression of Tcra locus recombination events and selection of a robust Tcra repertoire.
AB - Despite the longstanding correlation between transcription and variable-(diversity)-joining (V(D)J) recombination, it is unknown whether transcription itself can direct recombinase targeting. Here we show that blockade of transcriptional elongation through the mouse T cell receptor-alpha (Tcra) locus suppressed V(alpha)-to-J(alpha) recombination and chromatin remodeling of J(alpha) segments. Transcriptional blockade also derepressed cryptic J(alpha) promoters. Our results demonstrate two key functions for transcription in Tcra locus regulation. Transcription increases the recombination of J(alpha) segments located within several kilobases of a promoter and prevents the activation of downstream promoters through transcriptional interference. These influences promote an ordered progression of Tcra locus recombination events and selection of a robust Tcra repertoire.
U2 - 10.1038/ni1379
DO - 10.1038/ni1379
M3 - Journal article
C2 - 16936730
VL - 7
SP - 1109
EP - 1115
JO - Nature Immunology
JF - Nature Immunology
SN - 1529-2908
IS - 10
ER -
ID: 5238065