Transcriptional regulation of class-I major histocompatibility complex genes transformed in murine cells is mediated by positive and negative regulatory elements.
The expression of class-I major histocompatibility complex (MHC) antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low or absent; a phenotype that correlates with the high tumorigenicity of these cell lines. In primary mouse embryonal fibroblasts (MEF) from class-I transgenic mice (PD1 transgenic mice), Ad12-mediated transformation results in down-regulation of both endogenous genes and the transgene. Functional analysis of class-I regulatory elements revealed that the suppression of a class-I promoter is mediated by two negative regulatory elements, one of which functions specifically in Ad12-transformed cells. In addition, Ad12-transformed cells produce only minute amounts of the nuclear factors that bind to the major class-I enhancer, RI (region I or H2TF1). A silencer element derived from the 5' region of the miniature swine class-I gene (PD1) is capable of competing for the binding of nuclear factors to a second enhancer, RII (region II or CREII), that is located upstream from RI in the class-I regulatory element (CRE). Based on these results, we propose that down-regulation of class-I genes in Ad12-transformed cells is mediated mainly by negative regulators.
Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel.
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Rotem-Yehudar
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Shechter
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Ehrlich
D000256:Adenoviridae; D000818:Animals; D001667:Binding, Competitive; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D006183:H-2 Antigens