ROR gamma T, a thymus-specific isoform of the orphan nuclear receptor ROR gamma/TOR, is up-regulated by signaling through the pre-T cell receptor andbinds to the TEA promoter

TEA CT early alpha) is a genetic element located upstream of the TCR-J alph a cluster. Thymocytes from mice carrying a targeted deletion of TEA do not rearrange their TCR alpha locus on a window spanning the first nine J alpha segments. This led us to the hypothesis of TEA having a "rearrangement foc using" activity on the 5' side of the TCR-J alpha region. We analyzed DNAse l and "phylogenetic" footprints within the TEA promoter in an attempt to id entify trans-acting factors that could account for its regulatory function on DNA accessibility. One of these footprints corresponded to a putative DN A-binding site for an orphan nuclear receptor of the ROR/RZR family. The RO R gamma T cDNA clone was isolated from a thymus library using a probe corre sponding to the DNA-binding domain of ROR gamma/TOR. ROR gamma T is a thymu s-specific isoform of ROR gamma, expressed almost exclusively in immature d ouble-positive thymocytes. ROR gamma T binds, to the TEA promoter in vitro. Lastly, the expression of ROR gamma T is stimulated in two situations that mimic activation through the pre-TOP and in which the thymocytes have thei r TCR-alpha locus in an "open", yet unrearranged DNA configuration. We prop ose that the expression of ROR gamma T may be part of the pre-TCR activatio n cascade leading to the maturation of alpha/beta T cells and may participa te in the regulation of DNA accessibility in the TCR-J alpha focus.