Ludwig Institute for Cancer Research, Brussels, Belgium.
de Duve Institute, Université catholique de Louvain, Brussels, Belgium.
Immun Inflamm Dis. 2017 Sep;5(3):346-354. doi: 10.1002/iid3.172. Epub 2017 May 15.
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.
cDNA sequencing, promoter, and gene expression analyses were used to characterize the new transcript.
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.
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.
虽然大多数源自人类 T 细胞受体基因座的转录本反映了完全重排的基因,但已经鉴定出几种胚系转录本。我们描述了一种源自人类 TCRB 基因座的新的胚系转录本。
使用 cDNA 测序、启动子和基因表达分析来表征新的转录本。
源自人类 TCRB 基因座的新胚系转录本由 103bp 的新外显子组成,我们将其命名为 TRBX1 (X1),与基因片段 Cß1 或 Cß2 的第一个外显子拼接。X1 位于基因片段 Dß1 的上游,因此从 V-DJ 重排的 TCRB 基因座中缺失。X1-Cß 转录本似乎不编码蛋白质。我们定义了它们的转录起始点和最小启动子。这些转录本存在于血液或组织中的成熟 T 淋巴细胞群体以及单等位基因 TCRB 重排的 T 细胞克隆中。在未成熟的胸腺细胞中,它们已经可以在 CD1a CD34 CD4 CD8 细胞中检测到,因此在 TCRB 重排完成之前。
X1 启动子似乎是小鼠 pre-Dß1 启动子 (PDß1) 的同源物。与 PDß1 一样,其激活受 T 细胞中的 Eß 调节,并且通过有助于 Dß1 基因座的可及性,可能促进 TCRB 重排过程。