کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2832505 1163839 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Functional overlap in the cis-acting regulation of the V(D)J recombination at the TCRβ locus
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
Functional overlap in the cis-acting regulation of the V(D)J recombination at the TCRβ locus
چکیده انگلیسی

The second exon of lymphocyte antigen receptor genes is assembled in developing lymphocytes from component V, J and, in some cases, D gene segments through the process of V(D)J recombination. This process is initiated by an endonuclease comprised of the Rag-1 and Rag-2 proteins, collectively referred to as Rag. Rag binds to recombination signals (RSs) and catalyzes the pair-wise introduction of DNA double strand breaks (DSBs) at recombining gene segments. DNA cleavage by Rag is restricted both by intrinsic features of RSs, as well as the activity of other cis-acting elements, such as promoters and enhancers that regulate the accessibility of gene segments to Rag. In the TCRβ locus, accessibility of the Dβ1–Jβ1 gene segment cluster relies on the function of an enhancer, Eβ, and a promoter, PDβ1. Here we demonstrate that deletion of a small genomic region containing five of the six Jβ1 gene segments, but no known transcriptional regulatory elements, leads to a marked decrease in transcription and rearrangements involving the Dβ1 and Jβ1.1 gene segments. Surprisingly, point mutations in the RS of the Jβ1.1 gene segment not only impact Rag cleavage, but also lead to diminished transcription through the Dβ1–Jβ1 gene segment cluster. Our findings demonstrate that cis-acting elements that regulate transcription and accessibility of the TCRβ locus may functionally overlap with RS sequences, which are known primarily to direct Rag-mediated cleavage.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 46, Issue 3, January 2009, Pages 321–326
نویسندگان
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