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.
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.
Villey
I
I
Développement Normal et Pathologique du Système Immunitaire INSERM U429, Hôpital Necker Enfants Malades, Paris, France.
de Chasseval
R
R
de Villartay
J P
JP
D026923:Amino Acid Transport Systems, Basic; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology*; D005803:Genes, Immunoglobulin; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011401:Promoter Regions, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology
D026923:Amino Acid Transport Systems, Basic; D002352:Carrier Proteins; D008565:Membrane Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; C087435:Slc7a2 protein, mouse