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

Rodríguez-Caparrós, Alonso; Álvarez-Santiago, Jesús; del Valle-Pastor, María Jesús; Suñé, Carlos; López-Ros, Jennifer; Hernández-Munain, Cristina

doi:10.3390/ijms21228478

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

by

Alonso Rodríguez-Caparrós

,

Jesús Álvarez-Santiago

,

María Jesús del Valle-Pastor

,

Carlos Suñé

,

Jennifer López-Ros

and

Cristina Hernández-Munain

^*

Institute of Parasitology and Biomedicine “López-Neyra”—Spanish Scientific Research Council (IPBLN-CSIC), Parque Tecnológico de Ciencias de la Salud (PTS), 18016 Granada, Spain

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2020, 21(22), 8478; https://doi.org/10.3390/ijms21228478

Submission received: 12 October 2020 / Revised: 29 October 2020 / Accepted: 4 November 2020 / Published: 11 November 2020

(This article belongs to the Special Issue T Lymphocytes Biology, Pathogenesis and Therapeutic Applications)

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Abstract

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.

Keywords: T-cell receptor; enhancer; transcription; V(D)J recombination; chromatin; T-cell development

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MDPI and ACS Style

Rodríguez-Caparrós, A.; Álvarez-Santiago, J.; del Valle-Pastor, M.J.; Suñé, C.; López-Ros, J.; Hernández-Munain, C. Regulation of T-cell Receptor Gene Expression by Three-Dimensional Locus Conformation and Enhancer Function. Int. J. Mol. Sci. 2020, 21, 8478. https://doi.org/10.3390/ijms21228478

AMA Style

Rodríguez-Caparrós A, Álvarez-Santiago J, del Valle-Pastor MJ, Suñé C, López-Ros J, Hernández-Munain C. Regulation of T-cell Receptor Gene Expression by Three-Dimensional Locus Conformation and Enhancer Function. International Journal of Molecular Sciences. 2020; 21(22):8478. https://doi.org/10.3390/ijms21228478

Chicago/Turabian Style

Rodríguez-Caparrós, Alonso, Jesús Álvarez-Santiago, María Jesús del Valle-Pastor, Carlos Suñé, Jennifer López-Ros, and Cristina Hernández-Munain. 2020. "Regulation of T-cell Receptor Gene Expression by Three-Dimensional Locus Conformation and Enhancer Function" International Journal of Molecular Sciences 21, no. 22: 8478. https://doi.org/10.3390/ijms21228478

APA Style

Rodríguez-Caparrós, A., Álvarez-Santiago, J., del Valle-Pastor, M. J., Suñé, C., López-Ros, J., & Hernández-Munain, C. (2020). Regulation of T-cell Receptor Gene Expression by Three-Dimensional Locus Conformation and Enhancer Function. International Journal of Molecular Sciences, 21(22), 8478. https://doi.org/10.3390/ijms21228478

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

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