Developmental regulation of TCRδ locus accessibility and expression by the TCRδ enhancer
Academic ArticleArticle
Overview
MeSH Major
Cell Cycle Proteins
DNA-Activated Protein Kinase
DNA-Binding Proteins
Protein-Serine-Threonine Kinases
Recombination, Genetic
Tumor Suppressor Proteins
abstract
We have used gene-targeted mutation to assess the role of the T cell receptor delta (TCR delta) enhancer (E delta) in alphabeta and gammadelta T cell development. Mice lacking E delta exhibited no defects in alphabeta T cell development but had a severe reduction in thymic and peripheral gammadelta T cells and decreased VDJ delta rearrangements. Simultaneous deletion of both E delta and the TCR alpha enhancer (E alpha) demonstrated that residual TCR delta rearrangements were not driven by E alpha, implicating additional elements in TCR delta locus accessibility. Surprisingly, while deletion of E delta severely impaired germline TCR delta expression in double-negative thymocytes, absence of E delta did not affect expression of mature delta transcripts in gammadelta T cells. We conclude that E delta has an important role in TCR delta locus regulation at early, but not late, stages of gammadelta T cell development.
