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Integrated expression profiling and genome-wide analysis of ChREBP targets reveals the dual role for ChREBP in glucose-regulated gene expression

 Yun-Seung Jeong  ;  Deokhoon Kim  ;  Yong Seok Lee  ;  Ha-Jung Kim  ;  Jung-Youn Han  ;  Seung-Soon Im  ;  Hansook Kim Chong  ;  Je-Keun Kwon  ;  Yun-Ho Cho  ;  Woo Kyung Kim  ;  Timothy F. Osborne  ;  Jay D. Horton  ;  Hee-Sook Jun  ;  Yong-Ho Ahn  ;  Sung-Min Ahn  ;  Ji-Young Cha 
 PLOS ONE, Vol.6(7) : e22544, 2011 
Journal Title
Issue Date
Base Sequence ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism* ; Binding Sites ; Chromatin Immunoprecipitation ; DNA/metabolism ; Databases, Genetic ; Gene Expression Profiling* ; Gene Expression Regulation/drug effects* ; Genetic Loci/genetics ; Genome, Human/genetics* ; Glucose/pharmacology* ; HEK293 Cells ; Hep G2 Cells ; Humans ; Lipogenesis/drug effects ; Lipogenesis/genetics ; Liver/drug effects ; Liver/metabolism ; Molecular Sequence Data ; Protein Binding/drug effects ; Reproducibility of Results ; Signal Transduction/drug effects ; Signal Transduction/genetics
The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
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