RORgammaT, a thymus-specific isoform of the orphan nuclear receptor RORgamma / TOR, is up-regulated by signaling through the pre-T cell receptor and binds to the TEA promoter

Eur J Immunol. 1999 Dec;29(12):4072-80. doi: 10.1002/(SICI)1521-4141(199912)29:12<4072::AID-IMMU4072>3.0.CO;2-E.

Abstract

TEA (T early alpha) is a genetic element located upstream of the TCR-Jalpha cluster. Thymocytes from mice carrying a targeted deletion of TEA do not rearrange their TCRalpha locus on a window spanning the first nine Jalpha segments. This led us to the hypothesis of TEA having a "rearrangement focusing" activity on the 5' side of the TCR-Jalpha region. We analyzed DNAseI and "phylogenetic" footprints within the TEA promoter in an attempt to identify trans-acting factors that could account for its regulatory function on DNA accessibility. One of these footprints corresponded to a putative DNA-binding site for an orphan nuclear receptor of the ROR / RZR family. The RORgammaT cDNA clone was isolated from a thymus library using a probe corresponding to the DNA-binding domain of RORgamma / TOR. RORgammaT is a thymus-specific isoform of RORgamma, expressed almost exclusively in immature double-positive thymocytes. RORgammaT binds, to the TEA promoter in vitro. Lastly, the expression of RORgammaT is stimulated in two situations that mimic activation through the pre-TCR and in which the thymocytes have their TCR-alpha locus in an "open", yet unrearranged DNA configuration. We propose that the expression of RORgammaT may be part of the pre-TCR activation cascade leading to the maturation of alpha / beta T cells and may participate in the regulation of DNA accessibility in the TCR-Jalpha locus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport Systems, Basic*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Genes, Immunoglobulin
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Promoter Regions, Genetic
  • Receptors, Antigen, T-Cell, alpha-beta / genetics
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • Receptors, Cytoplasmic and Nuclear / immunology*
  • Receptors, Retinoic Acid*
  • Receptors, Thyroid Hormone*
  • Signal Transduction / immunology*
  • T-Lymphocytes / immunology*
  • Thymus Gland / immunology*
  • Up-Regulation / immunology

Substances

  • Amino Acid Transport Systems, Basic
  • Carrier Proteins
  • Membrane Proteins
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RORC protein, human
  • Receptors, Antigen, T-Cell, alpha-beta
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Retinoic Acid
  • Receptors, Thyroid Hormone
  • Rorc protein, mouse
  • Slc7a2 protein, mouse

Associated data

  • GENBANK/AJ131723
  • GENBANK/AJ132394