The human cathepsin D-encoding gene is transcribed from an estrogen-regulated and a constitutive start point.
The 5' flanking sequences, exon 1 and part of intron 1 of the human cathepsin D (CTD)-encoding gene (CTD) have been cloned and sequenced. RNase protection experiments identified two major transcription start points (tsp) located 14 and 63 nucleotides upstream of the start codon. The proximal -14, but not the distal -63 tsp has upstream near-concensus TATAAA and CCAAT sequences. Estrogens increase transcription from the -14 tsp, but not the -63 tsp and CTD is therefore unique among estrogen-regulated genes in having estrogen-regulated and constitutive transcription. Sequencing approximately 800 bp upstream and 600 bp downstream of the tsp failed to identify a consensus 13-bp palindromic estrogen-response element (ERE); however, four half-palindrome GGTCA motifs were located within 340 bp upstream of the -14 bp tsp. Thus, estrogen regulation of CTD may not be mediated by a consensus ERE.
May
F E
FE
University Department of Pathology, Royal Victoria Infirmary, Newcastle upon Tyne, UK.
Smith
D J
DJ
Westley
B R
BR
D001483:Base Sequence; D002402:Cathepsin D / Q000235:genetics*; D003001:Cloning, Molecular; D004247:DNA; D004967:Estrogens / Q000502:physiology*; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004967:Estrogens; D004247:DNA; D002402:Cathepsin D