The promoter region of the human type‐I‐DNA‐topoisomerase gene

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Abstract
We examined the promoter of the human type‐I‐DNA topoisomerase gene (hTOP1) for regions protected against DNase I digestion by nuclear proteins from HeLa or from adenovirus‐transformed 293 cells. We identified ten protected DNA sequences within 580 bp of DNA upstream of the transcriptional‐start sites and one additional site, which is located between the two clusters of transcriptional‐start sites. Several of these protein‐binding sites have significant similarities to recognition sequences of known transcription factors including factors Sp1, octamer transcription factor, cAMP‐responsive‐element‐binding protein (CREB/ATF), NF‐kB and members of the Myc‐related family of basic/helix‐loop‐helix/leucine‐zipper proteins. Other protein‐binding sites show less or no similarities to known consensus sequences. We investigated the physiological significance of these protein‐binding sites using a set of deletion and nucleotide‐exchange mutants. We conclude that the expression of the hTOP1 gene is regulated by a complex network of negatively and positively acting transcription factors.