title: Expression of the plasma prekallikrein gene: utilization of multiple transcription start sites and alternative promoter regions.
abstract: The plasma prekallikrein gene is expressed in many different human tissues at distinctly different levels and therefore tissue-specific control of the gene transcription is likely. In this study we demonstrate that transcription of the plasma prekallikrein gene can be initiated at multiple sites, for which at least four different promoters are utilized. A comparison of the genomic and mRNA sequences of mouse plasma prekallikrein revealed that the sequence segment that was formerly regarded as the first exon of the mouse plasma prekallikrein gene consists of three exons, with the first exon localized 14.2 kbp upstream of the translation start. For the rat and human plasma prekallikrein genes, in silico analysis suggested an analogous exon-intron organization. Determination of the transcription start sites showed that in both mouse and human, the proximal and distal regions could be utilized for transcription initiation; however, the proximal region is preferred. A deletion mutation analysis of the proximal promoter region using a 1.7-kbp segment revealed a strong activating region immediately upstream of the known mRNA, followed by both a modest repressor and an enhancer region.
authors.affiliation: Abteilung für Klinische Chemie und Klinische Biochemie, Chirurgische Klinik Innenstadt, Ludwig-Maximilians-Universität München, Nussbaumstrasse 20, D-80336 Münich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Neth
authors.forename: Marianne
authors.initials: M
authors.lastname: Arnhold
authors.forename: Viktoryia
authors.initials: V
authors.lastname: Sidarovich
authors.forename: Kanti D
authors.initials: KD
authors.lastname: Bhoola
authors.forename: Edwin
authors.initials: E
authors.lastname: Fink
mesh_terms: D020121:5' Untranslated Regions; D017398:Alternative Splicing; D000818:Animals; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D010179:Pancreas / Q000378:metabolism; D011288:Prekallikrein / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017384:Sequence Deletion; D024363:Transcription Initiation Site
chemical_list: D020121:5' Untranslated Regions; D012333:RNA, Messenger; D011288:Prekallikrein