An enhancer with cell-type dependent activity is located between the myeloid and epithelial aminopeptidase N (CD 13) promoters.
The 5' flanking region of the gene encoding the small intestinal brush-border peptidase aminopeptidase N (APN) was screened for the presence of enhancer regions. A 300 bp region with enhancer activity was identified 2.7 kb upstream of the transcriptional start site which is used in epithelial cells. The enhancer stimulated transcription from a heterologous promoter (the simian virus 40 early promoter) in a position- and orientation-independent manner. The activity of the enhancer is cell-type dependent and it is active in liver (HepG2), intestinal (Caco-2) and myeloid (K562) cells. As the epithelial APN promoter is active in the first two cell-types and the myeloid APN promoter in the last, the results may suggest that the enhancer, through a cooperation with either of the promoters, is important for the tissue-specific expression of APN. A detailed analysis of the enhancer led to the identification of four functionally important regions that are protected against DNase I digestion by Caco-2 nuclear extract. Sequence analysis suggests that two of the regions may interact with members of the Ets transcription factor family (Ets is a transformation-specific protein first discovered in the E26 avian erythroblastosis virus), one region with a CCAAT enhancer-binding protein and one region with Sp1, a transcriptional activator first described as a factor binding to the simian virus 40 early promoter.
Olsen
J
J
Department of Medical Biochemistry and Genetics, Biochemistry Laboratory C, The Panum Institute, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.
Kokholm
K
K
Troelsen
J T
JT
Laustsen
L
L
D001483:Base Sequence; D018826:CD13 Antigens / Q000235:genetics*; D018938:Caco-2 Cells; D002874:Chromosome Mapping; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D004848:Epithelium; D006367:HeLa Cells; D006801:Humans; D007962:Leukocytes; D008969:Molecular Sequence Data; D009928:Organ Specificity; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017422:Sequence Analysis, DNA
D018826:CD13 Antigens