RORγT, a thymus-specific isoform of the orphan nuclear receptor RORγ / TOR, is up-regulated by signaling through the pre-T cell receptor and binds to the TEA promoter
✍ Scribed by Isabelle Villey; Régina de Chasseval; Jean-Pierre de Villartay
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 151 KB
- Volume
- 29
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
TEA (T early alpha) is a genetic element located upstream of the TCR-J § cluster. Thymocytes from mice carrying a targeted deletion of TEA do not rearrange their TCR § locus on a window spanning the first nine J § segments. This led us to the hypothesis of TEA having a "rearrangement focusing" activity on the 5' side of the TCR-J § 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 ROR + T cDNA clone was isolated from a thymus library using a probe corresponding to the DNA-binding domain of ROR + /TOR. ROR + T is a thymus-specific isoform of ROR + , expressed almost exclusively in immature double-positive thymocytes. ROR + T binds, to the TEA promoter in vitro. Lastly, the expression of ROR + T is stimulated in two situations that mimic activation through the pre-TCR and in which the thymocytes have their TCR- § locus in an "open", yet unrearranged DNA configuration. We propose that the expression of ROR + T may be part of the pre-TCR activation cascade leading to the maturation of § / g T cells and may participate in the regulation of DNA accessibility in the TCR-J § locus.