Assessing a role for enhancer-blocking activity in gene regulation within the murine T-cell receptor α/δ locus

Academic Article

Abstract

  • Although situated close together within the T-cell receptor (TCR) α/δ locus, TCR δ and TCR α gene segments are controlled by two developmental stage-specific enhancers and are activated according to distinct developmental programmes. We previously used a stable transfection colony assay to identify an enhancer-blocking element, blocking element alpha/delta-1 (BEAD-1), between the TCR δ and α gene segments of the human TCR α/δ locus. We hypothesized that enhancer-blocking by BEAD-1 might be required to prevent the TCR δ enhancer from activating TCR α gene segment transcription and rearrangement at the double negative stage of thymocyte development. Here, we used a transfection approach to define partial enhancer-blocking activity in an analogous position of the murine TCR α/δ locus. To test the functional significance of this activity in vivo, we used gene targeting to delete the region from the endogenous locus. We found no perturbation of TCR δ and TCR α gene expression and rearrangement on targeted alleles, indicating that enhancer-blocking activity in this region is not required to maintain the developmentally distinct activation profiles of the two genes. We suggest that appropriate regulation may be achieved as a result of intrinsic biases in enhancer-promoter interactions or a developmental stage specificity to promoter function that is distinct from any additional specificity imposed by the enhancers themselves.
  • Authors

    Published In

  • Immunology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Sleckman BP; Carabana J; Zhong X; Krangel MS
  • Start Page

  • 11
  • End Page

  • 18
  • Volume

  • 104
  • Issue

  • 1