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Alternative Usages of Multiple Promoters of the Acetyl-CoA Carboxylase β Gene Are Related to Differential Transcriptional Regulation in Human and Rodent Tissues

Authors
 So-Young Oh  ;  Min-Young Lee  ;  Jong-Min Kim  ;  Sarah Yoon  ;  Soonah Shin  ;  Young Nyun Park  ;  Yong-Ho Ahn  ;  Kyung-Sup Kim 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.280(7) : 5909-5916, 2005 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2005
MeSH
5' Untranslated Regions/analysis ; 5' Untranslated Regions/genetics ; Acetyl-CoA Carboxylase/genetics* ; Animals ; Base Sequence ; Cell Line ; Conserved Sequence ; CpG Islands/genetics ; DNA-Binding Proteins/metabolism ; Diet ; Exons/genetics ; GATA4 Transcription Factor ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/genetics* ; Humans ; Liver/drug effects ; Liver/metabolism ; Male ; Mice ; Molecular Sequence Data ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/metabolism ; Myocardium/metabolism ; Myogenic Regulatory Factors/metabolism ; Organ Specificity ; Promoter Regions, Genetic/genetics* ; Rats ; Rats, Sprague-Dawley ; Receptors, Retinoic Acid/metabolism ; Transcription Factors/metabolism ; Transcription Initiation Site ; Transcription, Genetic/drug effects ; Transcription, Genetic/genetics*
Keywords
15590647
Abstract
Acetyl-CoA carboxylase beta (ACCbeta) is a critical enzyme in the regulation of fatty acid oxidation and is dominantly expressed in the skeletal muscle, heart, and liver. It has been established that two promoters, P-I and P-II, control the transcription of the ACCbeta gene. However, the precise mechanism involved in controlling tissue-specific gene expression of ACCbeta is largely unknown yet. In this study we revealed that promoter P-I, active in the skeletal muscle and heart but not in the liver, could be activated by myogenic regulatory factors and retinoid X receptors in a synergistic manner. Moreover, P-I was also activated markedly by the cardiac-specific transcription factors, Csx/Nkx2.5 and GATA4. These results suggest that the proper stimulation of P-I by these tissue-specific transcription factors is important for the expression of ACCbeta according to the tissue types. In addition, CpG sites around human exon 1a transcribed by P-I are half-methylated in muscle but completely methylated in the liver, where P-I is absolutely inactive. In humans, the skeletal muscle uses P-II as well as P-I, whereas only P-I is active in rat skeletal muscle. The proximal myogenic regulatory factor-binding sites in human P-II, which are not conserved in rat P-II, might contribute to this difference in P-II usage between human and rat skeletal muscle. Hepatoma-derived cell lines primarily use another novel promoter located about 3 kilobases upstream of P-I, designated as P-O. This study is the first to explain the mechanisms underlying the differential regulation of ACCbeta gene expression between tissues in living organisms.
Files in This Item:
T200500308.pdf Download
DOI
10.1074/jbc.M409037200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sup(김경섭) ORCID logo https://orcid.org/0000-0001-8483-8537
Kim, Jong Min(김종민)
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Shin, Soonah(신순아)
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
Oh, So Young(오소영)
Yoon, Sa Rah(윤사라)
Lee, Min Young(이민영)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/147554
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