A developmental switch from TCR delta enhancer to TCR alpha enhancer function during thymocyte maturation

Immunity. 1999 Jun;10(6):723-33. doi: 10.1016/s1074-7613(00)80071-0.

Abstract

V(D)J recombination and transcription within the TCR alpha/delta locus are regulated by three characterized cis-acting elements: the TCR delta enhancer (Edelta), TCR alpha enhancer (Ealpha), and T early alpha (TEA) promoter. Analysis of enhancer and promoter occupancy and function in developing thymocytes in vivo indicates Edelta and Ealpha to be developmental-stage-specific enhancers, with Edelta "on" and Ealpha "off" in double-negative III thymocytes and Edelta "off" and Ealpha "on" in double-positive thymocytes. Edelta downregulation reflects a loss of occupancy. Surprisingly, Ealpha and TEA are extensively occupied even prior to activation. TCR delta downregulation in double-positive thymocytes depends on two events, Edelta inactivation and removal of TCR delta from the influence of Ealpha by chromosomal excision.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / immunology
  • DNA Footprinting
  • Down-Regulation
  • Enhancer Elements, Genetic / immunology*
  • Genes, Switch / immunology*
  • Genes, T-Cell Receptor alpha / immunology*
  • Genes, T-Cell Receptor delta / immunology*
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Promoter Regions, Genetic / immunology
  • Recombination, Genetic
  • T-Lymphocyte Subsets / cytology*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Thymus Gland / cytology*
  • Thymus Gland / immunology
  • Thymus Gland / metabolism