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The roles of sterol regulatory element-binding proteins in the transactivation of the rat ATP citrate-lyase promoter

Authors
 Y A Moon  ;  J J Lee  ;  S W Park  ;  Y H Ahn  ;  K S Kim 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.275(39) : 30280-30286, 2000-09 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2000-09
MeSH
ATP Citrate (pro-S)-Lyase / genetics* ; Animals ; Binding Sites / genetics ; CCAAT-Binding Factor / metabolism ; CCAAT-Enhancer-Binding Proteins / metabolism* ; DNA Footprinting ; DNA-Binding Proteins / metabolism* ; Deoxyribonuclease I ; Humans ; Liver / enzymology ; Promoter Regions, Genetic ; Protein Binding ; Rats ; Sterol Regulatory Element Binding Protein 1 ; Sterol Regulatory Element Binding Protein 2 ; Transcription Factors / metabolism* ; Transcriptional Activation*
Abstract
ATP citrate-lyase (ACL) is a key enzyme supplying acetyl-CoA for fatty acid and cholesterol synthesis. Its expression is drastically up-regulated when an animal is fed a low fat, high carbohydrate diet after prolonged fasting. In this report, we describe the role of sterol regulatory element-binding proteins (SREBPs) in the transactivation of the rat ACL promoter. ACL promoter activity was markedly stimulated by the overexpression of SREBP-1a and, to a lesser extent, by SREBP-2 in Alexander human hepatoma cells. The promoter elements responsive to SREBPs were located within the 55-base pair sequences from -114 to -60. The gel mobility shift assay revealed four SREBP-1a binding sites in this region. Of these four elements, the -102/-94 region, immediately upstream of the inverted Y-box, and the -70/-61 region, just adjacent to Sp1 binding site, played critical roles in SREBPs-mediated stimulation. The mutation in the inverted Y-box and the coexpression of dominant negative nuclear factor-Y (NF-Y) significantly attenuated the transactivation by SREBP-1a, suggesting that NF-Y binding is a prerequisite for SREBPs to activate the ACL promoter. However, the multiple Sp1 binding sites did not affect the transactivation of the ACL promoter by SREBPs. The binding affinity of SREBP-1a to SREs of the ACL promoter also was much higher than that of SREBP-2. The transactivation potencies of the chimeric SREBPs, of which the activation domains (70 amino acids of the amino terminus) were derived from the different species of their carboxyl-terminal region, were similar to those of SREBPs corresponding to their carboxyl termini. Therefore, it is suggested that the carboxyl-terminal portions of SREBPs containing DNA binding domains are important in determining their transactivation potencies to a certain promoter.
Files in This Item:
T200003648.pdf Download
DOI
10.1074/jbc.M001066200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Park, Sahng Wook(박상욱) ORCID logo https://orcid.org/0000-0002-9594-7074
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/178714
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