1. Integrated Expression Profiling and Genome-Wide Analysis of ChREBP Targets Reveals the Dual Role for ChREBP in Glucose-Regulated Gene Expression
- Author
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Timothy F. Osborne, Yong-Ho Ahn, Yun Ho Cho, Hee-Sook Jun, Ji-Young Cha, Je Keun Kwon, Jung Youn Han, Woo Kyung Kim, Deokhoon Kim, Jay D. Horton, Seung Soon Im, Hansook Kim Chong, Sung-Min Ahn, Yun Seung Jeong, Yong-seok Lee, and Ha Jung Kim
- Subjects
Basic helix-loop-helix leucine zipper transcription factors ,dna-binding ,Biochemistry ,chip-seq data ,Databases, Genetic ,Molecular Cell Biology ,Gene expression ,Medicine and Health Sciences ,sites ,Signaling in Cellular Processes ,Genome Sequencing ,ob/ob mice ,transcription factor ,Genetics ,Regulation of gene expression ,Multidisciplinary ,Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ,Gene Ontologies ,Life Sciences ,Hep G2 Cells ,Genomics ,Chromatin ,Cell biology ,Liver ,Medicine ,Metabolic Pathways ,Protein Binding ,Signal Transduction ,Research Article ,Chromatin Immunoprecipitation ,Science ,Molecular Sequence Data ,DNA transcription ,binding protein ,Biology ,Glucose Signaling ,liver ,Molecular Genetics ,Metabolic Networks ,Genome Analysis Tools ,DNA-binding proteins ,Humans ,interacting protein ,Gene Regulation ,Gene ,Transcription factor ,center-dot-mlx ,Regulatory Networks ,Binding Sites ,Base Sequence ,Genome, Human ,Gene Expression Profiling ,Lipogenesis ,Reproducibility of Results ,Proteins ,Computational Biology ,Regulatory proteins ,DNA ,Comparative Genomics ,carbohydrate-response element ,Gene expression profiling ,Glucose ,HEK293 Cells ,Metabolism ,Gene Expression Regulation ,Genetic Loci ,Chromatin immunoprecipitation - Abstract
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.
- Published
- 2011