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

Young Ah Moon, Jae Jung Lee, Sahng Wook Park, Yong Ho Ahn, Kyung Sup Kim

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)30280-30286
Number of pages7
JournalJournal of Biological Chemistry
Volume275
Issue number39
StatePublished - Sep 29 2000

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ATP Citrate (pro-S)-Lyase
Sterol Regulatory Element Binding Proteins
Transcriptional Activation
Rats
Sterol Regulatory Element Binding Protein 1
Sterol Regulatory Element Binding Protein 2
Binding Sites
Acetyl Coenzyme A
High Fat Diet
Electrophoretic Mobility Shift Assay
Nutrition
Protein Binding
Base Pairing
Hepatocellular Carcinoma
Assays
Fasting
Animals
Fatty Acids
Gels
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

The roles of sterol regulatory element-binding proteins in the transactivation of the rat ATP citrate-lyase promoter. / Moon, Young Ah; Lee, Jae Jung; Park, Sahng Wook; Ahn, Yong Ho; Kim, Kyung Sup.

In: Journal of Biological Chemistry, Vol. 275, No. 39, 29.09.2000, p. 30280-30286.

Research output: Contribution to journalArticle

Moon, Young Ah ; Lee, Jae Jung ; Park, Sahng Wook ; Ahn, Yong Ho ; Kim, Kyung Sup. / The roles of sterol regulatory element-binding proteins in the transactivation of the rat ATP citrate-lyase promoter. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 39. pp. 30280-30286.
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