Promoter characterization and transcriptional regulation of Ncb5or, a novel reductase necessary for pancreatic beta-cell maintenance.
Ncb5or is a ubiquitously expressed gene required for beta-cell survival in mice. Examination of mouse tissues demonstrated high levels of expression in the pancreas, heart and kidney. A transcription start site was identified 149 bp upstream from the start codon and transient expression analysis in betaTC3 cells indicated the presence of a core promoter located within 348 bp upstream of this site. Deletion of Region C (-216/-157) resulted in a significant decrease in promoter activity and specific nucleotides located in a region designated C2 were demonstrated to be critical for complex binding. Deletion of Region D (-60/-33), which contains multiple consensus Sp1 sites, resulted in an additional loss of promoter activity. The data presented here identify and characterize the previously unknown promoter of Ncb5or, a reductase critical for beta-cell survival.
Larade
Kevin
K
Department of Medicine, Hematology Division, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, CHRB-05.215, Boston, MA 02115, USA.
Bunn
H Franklin
HF
D000818:Animals; D001483:Base Sequence; D002470:Cell Survival; D016384:Consensus Sequence; D042966:Cytochrome-B(5) Reductase / Q000235:genetics*; D005786:Gene Expression Regulation; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017384:Sequence Deletion; D014018:Tissue Distribution; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
C488723:Ncb5or protein, mouse; D042966:Cytochrome-B(5) Reductase