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 J alpha cluster (psi J alpha) is the site of an active rearrangement in the human thymus (delta Rec-psi J alpha 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 J alpha 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.
de Chasseval
R
R
Développement normal et pathologique du système immunitaire - INSERM U 132, Hôpital Necker-Enfants Malades, Paris, France.
de Villartay
J P
JP
D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism; D003850:Deoxyribonuclease I; D005786:Gene Expression Regulation; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D006801:Humans; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; D003850:Deoxyribonuclease I