Lactoferrin gene promoter in human and mouse. Analogous and dissimilar characteristics.
Lactoferrin promoter and the 5'-flanking region of both human and mouse were isolated from a genomic library constructed with lambda phage. A 2.0 kbp Sac I fragment of the human clone (HLF031a.30) and a 3.0 kbp Eco R I/Hinc II fragment of the mouse clone (mL14p9E) containing the lactoferrin promoter, 5'-flanking region, first exon and partial intron were sequenced completely. There were many sequence homologies between human and mouse at the promoter/enhancer (1 to -363) region, yet substantial divergence was observed beyond this region. To determine the promoter activity, 5'-deletion mutants of the mouse lactoferrin gene were linked to a CAT-reporter plasmid and transfected into the human endometrium carcinoma cell line, RL95-2. We identified a number of positive and negative regulatory sequences as well as the estrogen-response element in the 5'-flanking region of the lactoferrin gene. The imperfect estrogen response elements of both human and mouse are functional as demonstrated by transfection experiments, band-shift assay and DNase I footprint analysis. The molecular mechanism that governs the estrogen-stimulated response, however, differs between human and mouse.
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Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA.
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D016384:Consensus Sequence; D016889:Endometrial Neoplasms; D004742:Enhancer Elements, Genetic; D005260:Female; D015698:Genomic Library; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D007781:Lactoferrin / Q000235:genetics*; D051379:Mice / Q000235:genetics*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009838:Oligodeoxyribonucleotides; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping; D017384:Sequence Deletion; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection; D014407:Tumor Cells, Cultured; D014599:Uterus / Q000378:metabolism; D014981:Xenopus
D009838:Oligodeoxyribonucleotides; D015500:Chloramphenicol O-Acetyltransferase; D007781:Lactoferrin