title: Differential response of multiple epsilon-globin cap sites to cis- and trans-acting controls.
abstract: The human epsilon-globin gene has a number of alternative transcription-initiation sites located upstream of the canonical mRNA cap site. In three nonerythroid cell lines, "leaky" epsilon-globin transcription occurs exclusively from one of these upstream sites, the -200 cap site. Using a transient expression assay, we have shown that transcription initiation from the -200 cap site and the major cap site can be independently regulated in response to plasmid replication, SV40 enhancer sequences in cis, and the adenovirus E1A gene in trans. The -200 cap site is located within a region of S1 hypersensitivity in the supercoiled plasmid, and in the absence of viral enhancer sequences it is the main initiation site following transfection into a number of cell lines. We suggest that the -200 cap site acts as a polymerase entry site by virtue of its accessible chromatin structure. The efficiency of polymerase binding at this site may be altered by trans-acting regulatory molecules.
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics; D002460:Cell Line; D002874:Chromosome Mapping; D004261:DNA Replication; D004278:DNA, Superhelical / Q000235:genetics; D004720:Endonucleases; D005786:Gene Expression Regulation; D005814:Genes, Viral; D005914:Globins / Q000235:genetics*; D006801:Humans; D010957:Plasmids; D015719:Single-Strand Specific DNA and RNA Endonucleases; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D004278:DNA, Superhelical; D005914:Globins; D004720:Endonucleases; D015719:Single-Strand Specific DNA and RNA Endonucleases