PMID- 18505676 OWN - NLM STAT- MEDLINE DCOM- 20080724 LR - 20081121 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 372 IP - 4 DP - 2008 Aug 8 TI - Coordinate regulation of bovine prion protein gene promoter activity by two Sp1 binding site polymorphisms. PG - 530-5 LID - 10.1016/j.bbrc.2008.05.085 [doi] AB - Relationships between insertion/deletion (Ins/Del) polymorphisms of the bovine prion protein gene (PRNP) promoter and bovine spongiform encephalopathy (BSE) susceptibility have been reported. Our previous study has shown that polymorphisms of -6C-->T included in the specific protein 1 (Sp1) site in the 5'-flanking region of bovine PRNP influence the promoter activity of bovine PRNP. The present study shows that 12 and 23bp Ins/Del polymorphisms in the upstream region and an additional polymorphism (-47C-->A) in the Sp1 binding site coordinately affect the promoter activity. Reporter gene assays demonstrated that the bovine PRNP promoter containing -47A and 23bp Del/12bp Ins or 23bp Ins/12bp Ins showed lower promoter activity compared with other haplotypes (23bp Del/12bp Ins or 23bp Ins/12bp Del with -47C) or the wild-type haplotype (23bp Del/12bp Del with -47C). Furthermore, gel shift assays showed that the binding activity of Sp1 to the PRNP promoter was influenced by both polymorphisms with corresponding effects on the promoter activity. The coordinate regulation of the bovine PRNP promoter suggests the two Sp1 binding site polymorphisms control Sp1 binding to the PRNP promoter and its activity. FAU - Xue, Guangai AU - Xue G AD - Department of Molecular Immunology, School of Agricultural and Life Sciences, University of Tokyo, Bunkyo-ku Yayoi 1-1-1, Tokyo 113-8657, Japan. FAU - Sakudo, Akikazu AU - Sakudo A FAU - Kim, Chi-kyeong AU - Kim CK FAU - Onodera, Takashi AU - Onodera T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080527 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Prions) RN - 0 (Sp1 Transcription Factor) RN - EC 1.13.12.- (Luciferases) SB - IM MH - Animals MH - Base Sequence MH - Binding Sites/genetics MH - Cattle MH - DNA Mutational Analysis MH - Electrophoretic Mobility Shift Assay MH - Encephalopathy, Bovine Spongiform/*genetics MH - *Gene Expression Regulation MH - Genes, Reporter MH - *Genetic Predisposition to Disease MH - Haplotypes MH - INDEL Mutation MH - Luciferases/genetics MH - Molecular Sequence Data MH - *Polymorphism, Genetic MH - Prions/*genetics MH - Promoter Regions, Genetic MH - Sp1 Transcription Factor/*metabolism EDAT- 2008/05/29 09:00 MHDA- 2008/07/25 09:00 CRDT- 2008/05/29 09:00 PHST- 2008/05/09 00:00 [received] PHST- 2008/05/12 00:00 [accepted] PHST- 2008/05/29 09:00 [pubmed] PHST- 2008/07/25 09:00 [medline] PHST- 2008/05/29 09:00 [entrez] AID - S0006-291X(08)00956-X [pii] AID - 10.1016/j.bbrc.2008.05.085 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2008 Aug 8;372(4):530-5. doi: 10.1016/j.bbrc.2008.05.085. Epub 2008 May 27.