A new transcript in the TCRB locus unveils the human ortholog of the mouse pre‐Dß1 promoter. Issue 3 (15th May 2017)

• Record Type: Journal Article
• Authors: Lethé, Bernard; Snauwaert, Sylvia; Bricard, Orian; Schröder, David; Gomard, Tiphanie; Hames, Gérald; Muller, Catherine; Lurquin, Christophe; Gauthy, Emilie; Essaghir, Ahmed; Vandekerckhove, Bart; Coulie, Pierre G.
• Is Part Of: Immunity, inflammation and disease. Volume 5:Issue 3(2017)
• Page Start: 346
• Page End: 354
• Publication Date: 2017-05-15
• Subjects: Allelic inclusion -- human TCRB locus -- locus accessibility -- PDß1 germline transcripts -- T cells -- thymocytes -- TCRB transcripts; Immunology -- Periodicals; Immunity -- Periodicals; Inflammation -- Periodicals; 616.079
• DOI: 10.1002/iid3.172
• Languages: English
• ISSNs: 2050-4527

Abstract

Abstract: Introduction: While most transcripts arising from the human T Cell Receptor locus reflect fully rearranged genes, several germline transcripts have been identified. We describe a new germline transcript arising from the human TCRB locus. Methods: cDNA sequencing, promoter, and gene expression analyses were used to characterize the new transcript. Results: The new germline transcript encoded by the human TCRB locus consists of a new exon of 103 bp, which we named TRBX1 ( X1 ), spliced with the first exon of gene segments Cß1 or Cß2 . X1 is located upstream of gene segment Dß1 and is therefore deleted from a V‐DJ rearranged TCRB locus. The X1‐Cß transcripts do not appear to code for a protein. We define their transcription start and minimal promoter. These transcripts are found in populations of mature T lymphocytes from blood or tissues and in T cell clones with a monoallelic TCRB rearrangement. In immature thymocytes, they are already detectable in CD1a − CD34 + CD4 − CD8 − cells, therefore before completion of the TCRB rearrangements. Conclusions: The X1 promoter appears to be the ortholog of the mouse pre‐Dß1 promoter ( PDß1) . Like PDß1, its activation is regulated by Eß in T cells and might facilitate the TCRB rearrangement process by contributing to the accessibility of the Dß1 locus. Abstract : We describe new germline transcripts from the human TCRB locus. They contain a new exon, which we name X1. X1‐containing transcripts are the orthologs of the murine transcripts that are controlled by a promoter named PDB1. PDB1 is considered as an Accessibility Control Element for the murine TCRB locus and we surmise that the X1 promoter has a similar function in human T cells.