T cell receptor (TCR) α/δ locus enhancer identity and position are critical for the assembly of TCR δ and a variable region genes Academic Article uri icon

Overview

MeSH Major

  • Genes, T-Cell Receptor alpha
  • Genes, T-Cell Receptor delta
  • Lymphocytes

abstract

  • T cell receptor (TCR) delta and alpha variable region genes are assembled from germ-line gene segments located in a single chromosomal locus in which TCR delta segments are situated between TCR alpha segments. The TCR alpha enhancer (E alpha) located at the 3' end of the TCR alpha/delta locus functions over a long chromosomal distance to promote TCR alpha rearrangement and maximal TCR delta expression; whereas the TCR delta enhancer (E delta) is located among the TCR delta segments and functions with additional element(s) to mediate TCR delta rearrangement. We used gene-targeted mutation to evaluate whether the identity of E alpha and the position of E delta are critical for the developmental stage-specific assembly of TCR delta and alpha variable region genes. Specific replacement of E alpha with E delta, the core E alpha element (E alpha C), or the Ig heavy chain intronic enhancer (iE mu), all of which promote accessibility in the context of transgenic V(D)J recombination substrates, did not promote a significant level of TCR alpha rearrangement beyond that observed in the absence of E alpha. Therefore, the identity and full complement of E alpha-binding sites are critical for promoting accessibility within the TCR alpha locus. In the absence of the endogenous E delta element, specific replacement of E alpha with E delta also did not promote TCR delta rearrangement. However, deletion of intervening TCR alpha/delta locus sequences to restore the inserted E delta to its normal chromosomal position relative to 5' sequences rescued TCR delta rearrangement. Therefore, unlike E alpha, E delta lacks ability to function over the large intervening TCR alpha locus and or E delta function requires proximity to additional upstream element(s) to promote TCR delta accessibility.

publication date

  • March 4, 2003

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC151386

Digital Object Identifier (DOI)

  • 10.1073/pnas.0437943100

PubMed ID

  • 12604775

Additional Document Info

start page

  • 2598

end page

  • 603

volume

  • 100

number

  • 5