Developmental regulation of VDJ recombination by the core fragment of the T cell receptor alpha enhancer

J Exp Med. 1997 Jan 6;185(1):131-40. doi: 10.1084/jem.185.1.131.

Abstract

The role of T cell receptor alpha enhancer (E alpha) cis-acting elements in the developmental regulation of VDJ recombination at the TCR alpha/delta locus was examined in transgenic mice containing variants of a minilocus VDJ recombination substrate. We demonstrate that the 116-bp T alpha 1,2 core enhancer fragment of the 1.4-kb E alpha is sufficient to activate the enhancer-dependent step of minilocus rearrangement, and that within T alpha 1,2, intact binding sites for TCF/LEF and Ets family transcription factors are essential. Although minilocus rearrangement under the control of the 1.4-kb E alpha initiates at fetal day 16.5 and is strictly limited to alpha beta T cells, we find that rearrangement under the control of T alpha 1,2 initiates slightly earlier during ontogeny and occurs in both gamma delta and alpha beta T cells. We conclude that the core fragment of E alpha can establish accessibility to the recombinase in developing thymocytes in vivo in a fashion that is dependent on the binding of TCF/LEF and Ets family transcription factors, but that these and other factors that bind to the E alpha core cannot account for the precise developmental onset of accessibility that is provided by the intact E alpha. Rather, our data suggests a critical role for factors that bind E alpha outside of the core T alpha 1,2 region in establishing the precise developmental onset of TCR alpha rearrangement in vivo.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • DNA Nucleotidyltransferases / metabolism
  • DNA Primers
  • Enhancer Elements, Genetic*
  • Flow Cytometry
  • Gene Rearrangement, delta-Chain T-Cell Antigen Receptor*
  • Humans
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / biosynthesis
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • T-Lymphocytes / immunology*
  • VDJ Recombinases

Substances

  • DNA Primers
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Antigen, T-Cell, gamma-delta
  • DNA Nucleotidyltransferases
  • VDJ Recombinases