A new transcript in the TCRB locus unveils the human ortholog of the mouse pre‐Dß1 promoter

• Published in: Immunity, Inflammation and Disease Inflammation and Disease, 2017-09, Vol.5 (3), p.346-354
• Main 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.
• Format: Article
• Language: English
• Subjects: Allelic inclusion; Animals; Gene expression; Genes, T-Cell Receptor beta; Genetic Loci; human TCRB locus; Humans; locus accessibility; Mice; Original Research; PDß1 germline transcripts; Promoter Regions, Genetic; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; T cell receptors; T cells; TCRB transcripts; thymocytes; Transcription, Genetic
• ISSN: 2050-4527; 2050-4527
• DOI: 10.1002/iid3.172

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. 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.