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Cloning of Human Acetyl-CoA Carboxylase β Promoter and Its Regulation by Muscle Regulatory Factors

Authors
 Jae-Jung Lee  ;  Young-Ah Moon  ;  Joo-Hun Ha  ;  Do-Jun Yoon  ;  Yong-Ho Ahn  ;  Kyung-Sup Kim 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.276(4) : 2576-2585, 2001 
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
 0021-9258 
Issue Date
2001
MeSH
Acetyl-CoA Carboxylase/genetics* ; Base Sequence ; Binding Sites ; Cloning, Molecular ; Gene Expression Regulation, Enzymologic ; Gene Library ; Humans ; Molecular Sequence Data ; Muscle, Skeletal ; MyoD Protein/metabolism* ; Myogenic Regulatory Factors/metabolism* ; Promoter Regions, Genetic* ; Protein Binding
Abstract
The 280-kDa beta-isoform of acetyl-CoA carboxylase (ACCbeta) is predominantly expressed in heart and skeletal muscle, whereas the 265-kDa alpha-isoform (ACCalpha) is the major ACC in lipogenic tissues. The ACCbeta promoter showed myoblast-specific promoter activity and was strongly induced by MyoD in NIH3T3 cells. Serial deletions of the promoter revealed that MyoD acts on the E-boxes located at positions -498 to -403 and on the proximal region including the 5'-untranslated region. Destruction of the E-boxes at positions -498 to -403 by site-directed mutagenesis resulted in a significant decrease of MyoD responsiveness. The "TGAAA" at -32 to -28 and the region around the transcription start site play important roles in basal transcription, probably as a TATA box and an Inr element, respectively. Mutations of another E-box at -14 to -9 and a "GCCTGTCA" sequence at +17 to +24 drastically decreased the MyoD responsiveness. The novel cis-element GCCTGTCA was preferentially bound by MyoD homodimer in EMSA and conferred MyoD responsiveness to a luciferase reporter, which was repressed by the overexpression of E12. This finding is unique since activation via E-boxes is mediated by heterodimers of MyoD and E-proteins. We screened a human skeletal muscle cDNA library to isolate clones expressing proteins that bind to the region around the GCCTGTCA (+8 to +27) sequence, and isolated Myf4 and Myf6 cDNAs. Electrophoretic mobility shift assay showed that recombinant Myf4 and Myf6 bind to this novel cis-element. Moreover, transient expression of Myf6 induced significant activation on the ACCbeta promoter or an artificial promoter harboring this novel cis-element. These findings suggest that muscle regulatory factors, such as MyoD, Myf4, and Myf6, contribute to the muscle-specific expression of ACCbeta via E-boxes and the novel cis-element GCCTGTCA.
Files in This Item:
T200102634.pdf Download
DOI
10.1074/jbc.M007002200
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
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142612
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