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@ARTICLE{Schnberg:300201,
      author       = {P. Y. Schönberg and Á. Muñoz-Ovalle and M.
                      Paszkowski-Rogacz and E. Crespo and D. Sürün and A.
                      Feldmann$^*$ and F. Buchholz$^*$},
      title        = {{A} pooled {CRISPR} screen identifies the {T}α2 enhancer
                      element as a driver of {TRA} expression in a subset of
                      mature human {T} lymphocytes.},
      journal      = {Frontiers in immunology},
      volume       = {16},
      issn         = {1664-3224},
      address      = {Lausanne},
      publisher    = {Frontiers Media},
      reportid     = {DKFZ-2025-00678},
      pages        = {1536003},
      year         = {2025},
      abstract     = {The T cell receptor (TCR) is crucial for immune responses
                      and represents a pivotal therapeutic target for CAR T cell
                      therapies. However, which enhancer elements drive the
                      constitutive expression of the TCRα chain in mature,
                      peripheral T cells has not been well defined. Earlier work
                      has suggested that enhancer alpha is inactive in mature
                      peripheral T cells and that an alternative enhancer element
                      in the 5' J region was driving TRA expression, while more
                      recent findings indicated the opposite. Here, we applied a
                      pooled CRISPR screen to probe a large genomic region
                      proximal to the human TRA gene for the presence of
                      regulatory elements. Interestingly, no sgRNA targeting the
                      5' J region was identified that influenced TRA expression.
                      In contrast, several sgRNAs targeting enhancer alpha element
                      Tα2, were identified that compromised the expression of the
                      TCRα chain in Jurkat E6.1, as well as in a subset of human
                      primary T cells. Our results provide new insights into the
                      regulation of TRA in human peripheral T cells, advancing our
                      understanding of how constitutive TRA expression is driven
                      and regulated.},
      keywords     = {Humans / Enhancer Elements, Genetic / CRISPR-Cas Systems /
                      Jurkat Cells / Receptors, Antigen, T-Cell, alpha-beta:
                      genetics / T-Lymphocytes: immunology / T-Lymphocytes:
                      metabolism / Gene Expression Regulation / CAR T cells
                      (Other) / CRISPR screen (Other) / TCR expression (Other) /
                      TRA locus (Other) / TRA regulation (Other) / enhancer alpha
                      (Other) / genome editing (Other) / Receptors, Antigen,
                      T-Cell, alpha-beta (NLM Chemicals)},
      cin          = {DD01},
      ddc          = {610},
      cid          = {I:(DE-He78)DD01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40160815},
      pmc          = {pmc:PMC11949936},
      doi          = {10.3389/fimmu.2025.1536003},
      url          = {https://inrepo02.dkfz.de/record/300201},
}