Document Detail


Regulation of leptin promoter function by Sp1, C/EBP, and a novel factor.
MedLine Citation:
PMID:  9492033     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Leptin is a hormone produced in adipose cells that regulates energy expenditure, food intake, and adiposity. To understand leptin's transcriptional regulation, we are studying its promoter. Four conserved and functional regions were identified. Mutations in the C/EBP and TATA motifs each caused an approximately 10-fold decrease in promoter activity. The C/EBP motif bound recombinant C/EBP alpha and mediated trans-activation by C/EBP alpha, -beta, and -delta. Mutation of a consensus Sp1 site reduced promoter activity 2.5-fold and abolished binding of Sp1. Mutation of a fourth factor-binding site, denoted LP1, abolished protein binding and reduced promoter activity 2-fold. Factor binding to the LP1 motif was observed with adipocyte, but not with nonadipocyte extracts. Adipocytes from fa/fa Zucker rats transcribed the reporter plasmids more efficiently than did control adipocytes. No effect on the transient expression of leptin was noted upon treatment with a thiazolidinedione, BRL49653, or upon cotransfection with peroxisome proliferator-activated receptor-gamma/retinoid X receptor-alpha or sterol response element-binding protein-1. Mutations of the Sp1, LP1, and C/EBP sites in pairwise combinations diminished promoter activity to the extent predicted assuming these motifs contribute independently to leptin promoter function. Our identification of motifs regulating leptin transcription is an important step in the elucidation of the mechanisms underlying hormonal and metabolic regulation of this gene.
Authors:
M M Mason; Y He; H Chen; M J Quon; M Reitman
Related Documents :
8876643 - The mechanism of recruitment of the lactate dehydrogenase-b/epsilon-crystallin gene by ...
2692853 - A yeast ribosomal dna-binding protein that binds to the rdna enhancer and also close to...
24472243 - Species-dependent binding of tocainide analogues to albumin: affinity chromatography an...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  139     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1998 Mar 
Date Detail:
Created Date:  1998-03-12     Completed Date:  1998-03-12     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1013-22     Citation Subset:  AIM; IM    
Affiliation:
Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-1770, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adipocytes / metabolism
Animals
Base Sequence
Binding Sites
CCAAT-Enhancer-Binding Proteins
DNA-Binding Proteins / physiology*
Hela Cells
Humans
Leptin
Molecular Sequence Data
Nuclear Proteins / physiology*
Point Mutation
Promoter Regions, Genetic*
Proteins / genetics*
Rats
Rats, Zucker
Receptors, Cytoplasmic and Nuclear / physiology
Sp1 Transcription Factor / physiology*
Sterol Regulatory Element Binding Protein 1
Transcription Factors / physiology
Chemical
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Proteins; 0/DNA-Binding Proteins; 0/Leptin; 0/Nuclear Proteins; 0/Proteins; 0/Receptors, Cytoplasmic and Nuclear; 0/SREBF1 protein, human; 0/Sp1 Transcription Factor; 0/Srebf1 protein, rat; 0/Sterol Regulatory Element Binding Protein 1; 0/Transcription Factors

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Dexamethasone promotes expression of membrane-bound macrophage colony-stimulating factor in murine o...
Next Document:  Differential expression of calcitonin and parathyroid hormone/parathyroid hormone-related protein re...