Regulation of T-cell Receptor Gene Expression by Three-Dimensional Locus Conformation and Enhancer Function

• Published in: International journal of molecular sciences 2020-11, Vol.21 (22), p.8478
• Main Authors: Rodríguez-Caparrós, Alonso, Álvarez-Santiago, Jesús, Del Valle-Pastor, María Jesús, Suñé, Carlos, López-Ros, Jennifer, Hernández-Munain, Cristina
• Format: Article
• Language: English
• Subjects: Adaptive immunity; Animals; Antigens; Chromatin; Chromatin - genetics; Chromatin - immunology; Configurations; Conformation; enhancer; Enhancer Elements, Genetic - genetics; Enhancer Elements, Genetic - immunology; Enhancers; Gene expression; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Genes, T-Cell Receptor - genetics; Genes, T-Cell Receptor - immunology; Humans; Immune response; Lymphocytes; Lymphocytes T; Maturation; Pathogens; Peptides; Regulatory sequences; Review; Signal transduction; Signal Transduction - genetics; Signal Transduction - immunology; T cell receptors; T-cell development; T-cell receptor; T-Lymphocytes - immunology; Thymocytes; Thymus gland; Transcription; Transcription, Genetic - genetics; Transcription, Genetic - immunology; V(D)J recombination; V(D)J Recombination - genetics; V(D)J Recombination - immunology; Vertebrates
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21228478

The adaptive immune response in vertebrates depends on the expression of antigen-specific receptors in lymphocytes. T-cell receptor (TCR) gene expression is exquisitely regulated during thymocyte development to drive the generation of αβ and γδ T lymphocytes. The TCRα, TCRβ, TCRγ, and TCRδ genes exist in two different configurations, unrearranged and rearranged. A correctly rearranged configuration is required for expression of a functional TCR chain. TCRs can take the form of one of three possible heterodimers, pre-TCR, TCRαβ, or TCRγδ which drive thymocyte maturation into αβ or γδ T lymphocytes. To pass from an unrearranged to a rearranged configuration, global and local three dimensional (3D) chromatin changes must occur during thymocyte development to regulate gene segment accessibility for V(D)J recombination. During this process, enhancers play a critical role by modifying the chromatin conformation and triggering noncoding germline transcription that promotes the recruitment of the recombination machinery. The different signaling that thymocytes receive during their development controls enhancer activity. Here, we summarize the dynamics of long-distance interactions established through chromatin regulatory elements that drive transcription and V(D)J recombination and how different signaling pathways are orchestrated to regulate the activity of enhancers to precisely control TCR gene expression during T-cell maturation.