Document Detail


Transcriptional regulation of fatty acid synthase gene and ATP citrate-lyase gene by Sp1 and Sp3 in rat hepatocytes(1).
MedLine Citation:
PMID:  10618488     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
When two copies of the sequences spanning -57 to -35 of the fatty acid synthase (FAS) or -64 to -41 of the ATP citrate-lyase (ACL) gene linked to a reporter gene were transfected into primary cultured hepatocytes, the reporter activities significantly increased in response to insulin/glucose treatment. In cotransfection experiments of the FAS(-57/-35) with the Sp1 or Sp3 expression vector, the reporter activities of transcription were suppressed by Sp1 and stimulated by Sp3. In the cotransfection experiments of ACL(-64/-41), the activities were suppressed by Sp1 but were unchanged by Sp3. A similar effect of Sp1 and Sp3 on transcription was seen in mRNA concentrations and enzyme activities of endogenous FAS and ACL. Moreover, the mRNA concentrations and enzyme activities of endogenous acetyl-CoA carboxylase were suppressed by Sp1 and greatly increased by Sp3. Gel mobility super shift assays using antibodies against Sp1 or Sp3 revealed the binding of the transcription factors Sp1 and Sp3 with the GC rich regions located within FAS(-57/-35) and ACL(-64/-41) genes. The formation of DNA-protein complexes was decreased in rats fed a high-carbohydrate diet in comparison with that in fasted rats, but feeding the corn oil diet inhibited this decrease. In Western immunoblotting assay, however, the amount of Sp1 and Sp3 remained unchanged in the dietary conditions. Therefore, the binding of DNA-protein complexes was not due to changes in the amount of Sp1 and Sp3 but to changes in the binding activity, suggesting that these transcription factors may be an important determinant of lipogenic enzyme expression.
Authors:
H Fukuda; T Noguchi; N Iritani
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  FEBS letters     Volume:  464     ISSN:  0014-5793     ISO Abbreviation:  FEBS Lett.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-02-10     Completed Date:  2000-02-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0155157     Medline TA:  FEBS Lett     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  113-7     Citation Subset:  IM    
Affiliation:
Tezukayama Gakuin University, 4-cho, Harumidai, Sakai, Osaka, Japan.
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MeSH Terms
Descriptor/Qualifier:
ATP Citrate (pro-S)-Lyase / genetics*
Acetyl-CoA Carboxylase / genetics
Animals
Base Sequence
Blotting, Western
DNA Primers
DNA-Binding Proteins / metabolism*
Fatty Acid Synthetase Complex / genetics*
Gene Expression Regulation, Enzymologic*
Liver / cytology,  enzymology*
Male
RNA, Messenger / genetics
Rats
Rats, Wistar
Sp1 Transcription Factor / metabolism*
Sp3 Transcription Factor
Transcription Factors / metabolism*
Transcription, Genetic*
Chemical
Reg. No./Substance:
0/DNA Primers; 0/DNA-Binding Proteins; 0/RNA, Messenger; 0/Sp1 Transcription Factor; 0/Sp3 protein, rat; 0/Transcription Factors; 148710-94-5/Sp3 Transcription Factor; EC 2.3.3.8/ATP Citrate (pro-S)-Lyase; EC 6.-/Fatty Acid Synthetase Complex; EC 6.4.1.2/Acetyl-CoA Carboxylase

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


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