Nucleotide Sequence and Nuclease Hypersensitivity of the Chinese Hamster Dihydrofolate Reductase Gene Promoter Region

We have sequenced the 1240 base pairs (bp) upstream from the translation start site of the hamster dihydrofolate reductase (DHFR) gene. The DNA in the 5' flanking region contains several elements that are homologous in both sequence and relative location to corresponding elements in the human and murine DHFR genes: an 11-bp element adjacent to the ATG codon, a 19-bp element that coincides with the major transcription start site, and two 29-bp upstream elements that are represented 4 times in the murine DHFR gene but only once in the human gene. Two clusters of short, G/C-rich elements conforming to the consensus binding sequence for the transcription factor Spl are located in the upstream region in all three genes. The symmetrical placement of the G/C boxes coincides with a symmetrical DNase I hypersensitive pattern in the chromatin, suggesting that the Spl protein may be involved in maintaining chromatin structure in this region.