FUNCTIONAL-CHARACTERIZATION OF THE PROMOTER FOR THE HUMAN GERM-LINE T-CELL RECEPTOR J-ALPHA (TEA) TRANSCRIPT

The T cell receptor (TCR)-alpha and -delta loci are contained on the same chromosomal region, and yet are developmentally and genetically independent. The first element of the Jalpha cluster (psiJalpha) is the site of an active rearrangement in the human thymus (deltaRec-psiJalpha rearrangement) and is localized downstream of a region expressed as a germ-line sterile transcript (TEA) in the human developing thymus.We hypothesized that the transcription of TEA could be indicative of (or responsible for) the opening of the Jalpha to the V(D)J recombinase and undertook to analyze cis-acting sequences controlling the TEA transcription. The promoter of TEA was characterized. It was part of a region that is highly conserved between human and mouse and contained many sites for the putative binding of T cell-specific transcription factors. The in vitro activity of this promoter was dependent on the association with an enhancer. A strong DNase I hypersensitive site was found in the vicinity of this promoter again suggesting the possible presence of protein-DNA interactions in this region. The implications of these results in the general perspective of TCR-alpha/delta gene regulation is discussed.