The transcriptional activity of a muscle-specific promoter depends critically on the structure of the TATA element and its binding protein.
We have previously characterized the proximal promoter of the mouse IIB myosin heavy chain (MyHC) gene, which is expressed only in fast-contracting glycolytic skeletal muscle fibers. We show here that the substitution into this promoter of a non-canonical TATA sequence from the IgH gene results in inactivity in muscle cells, even though TATA-binding protein (TBP) can bind strongly to this mutated promoter. Chemical foot-printing data show, however, that TBP makes different DNA contacts on this heterologous TATA sequence. The inactivity of such a non-canonical TATA motif in the IIB promoter context appears to be caused by a non-functional conformation of the bound TBP-DNA complex that is incapable of sustaining transcription. The conclusions imply that the precise sequence of the promoter TATA motif needs to be matched with the specific functional class of upstream activator proteins present in a given cell type in order for the gene to be transcriptionally active.
Diagana
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Département de Biologie Moleulaire, Institut Pasteur, Paris, France. tdiagana@aim.salk.edu
North
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Jabet
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Fiszman
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Takeda
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Whalen
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D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018983:DNA Footprinting; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D019143:Evolution, Molecular; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D051379:Mice; D015394:Molecular Structure; D018482:Muscle, Skeletal / Q000378:metabolism; D009154:Mutation; D018995:Myosin Heavy Chains / Q000235:genetics*; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D016385:TATA Box; D035181:TATA-Box Binding Protein; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D004247:DNA; D018995:Myosin Heavy Chains