Functional analysis of the transcriptional activity of the mouse phospholipid transfer protein gene.
Phospholipid transfer protein (PLTP) plays an important role in the metabolism of plasma high density lipoprotein. The mouse gene encoding PLTP and its promoter region has been cloned in our laboratory. The present study was conducted to functionally analyze the transcriptional regulation of the mouse PLTP gene. The results indicated that DNA sequences between -245 and -69 were responsible for the full promoter activity and binding motifs for transcription factor Sp1 and AP-2 within this functional promoter region were synergistically essential for the basal transcription. The transcriptional activity of this gene was significantly increased by chenodeoxycholic acid and fenofibrate, suggesting that transcription factor farnesoid X-activated receptor (FXR) and peroxisome proliferator-activated receptor (PPAR) are likely involved in the transcriptional regulation. DNA sequence analysis suggests that DNA sequences from -407 to -395 and from -393 to -381 are homologous to the recognition motifs of FXR, and those from -859 to -847 and from -309 to -297 are similar to the potential binding motif for PPAR. These findings provide a molecular basis for further investigation of the physiological function and regulation of the PLTP gene in mice.
Tu
A Y
AY
Department of Medicine, Northwest Lipid Research Laboratories, University of Washington, 2121 N. 35th Street, Seattle, WA 98103, USA. aytu@u.washington.edu
Albers
J J
JJ
D020816:Amino Acid Motifs; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002635:Chenodeoxycholic Acid / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism; D011345:Fenofibrate / Q000494:pharmacology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D049294:Phospholipid Transfer Proteins; D011401:Promoter Regions, Genetic; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D006888:Hydroxycholesterols; C436492:KLF12 protein, human; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D002635:Chenodeoxycholic Acid; C003585:22-hydroxycholesterol; D011345:Fenofibrate