A dominant transcriptional silencer located 5' to the human T-cell receptor V beta 2.2 gene segment which is activated in cell lines of thymic phenotype.
We have identified a transcriptional regulatory sequence located 5' to the human T-cell receptor V beta 2.2 promoter. The upstream part of this sequence acts as a transcriptional activator in the three cell lines, Jurkat, MOLT4 and HSB2, which all have a thymic phenotype. The downstream part of the sequence exerts a dominant silencing activity in the Jurkat and MOLT4 cell lines, but not in the immature HSB2 cell line. The silencing sequence binds nuclear factor(s). Mutations of nucleotides in a short stretch of sequence, demonstrating methylation interference, abolish both the factor binding and the silencing effect. Replacement of the silencing element by a homologous sequence found 5' to the human V beta 8.1 segment, leads to a protein binding pattern which shows some DNA- protein specific complexes identical to those observed with the V beta 2.2 sequence. Interestingly, binding of nuclear factors to the V beta 2.2 silencing sequence is also observed using thymic extracts, but not using extracts from samples enriched for CD34+ cells, PBL, EBV cell lines or the HeLa cell line.
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Laboratory of Molecular Hematology, Centre Hayem, Saint-Louis Hospital, Paris, France.
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Sigaux
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D001483:Base Sequence; D004247:DNA; D004268:DNA-Binding Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D011401:Promoter Regions, Genetic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D013950:Thymus Gland / Q000166:cytology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D004247:DNA