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Biochim Biophys Acta. 1995 May 24;1271(1):127-34.

Human mitochondrial transcription factor A and promoter spacing integrity are required for transcription initiation.

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Department of Developmental Biology, Stanford University School of Medicine, CA 94305-5427, USA.


The two major promoters for transcription of the human mitochondrial genome are located near each other in the displacement-loop region of the molecule. Previous work has localized these promoters to regions of < 100 nucleotides each; the DNA sequence at the transcription start site is stringently required, as is the region from -10 to -40 base pairs upstream of each respective start site. Each upstream site is recognized and bound by human mitochondrial transcription factor A (h-mtTFA), an event previously shown to be important for transcriptional activation. We report here results using recombinant h-mtTFA that demonstrate the dependence of transcription initiation of h-mtTFA. In addition, altering the distance between the h-mtTFA binding site and the transcription start site greatly impairs transcription initiation efficiency. The decrease in transcription initiation efficiency was shown to be a consequence of altering the position of h-mtTFA binding as opposed to the strength of h-mtTFA binding, as judged by DNA footprinting ability. Analysis of a chimeric yeast-human promoter revealed that the yeast mtTFA homologue cannot substitute for the human protein, even when bound at an appropriate position upstream of the human transcription start site.

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