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

• Published in: PloS one 2011-07, Vol.6 (7), p.e22544
• Main Authors: Jeong, Yun-Seung, Kim, Deokhoon, Lee, Yong Seok, Kim, Ha-Jung, Han, Jung-Youn, Im, Seung-Soon, Chong, Hansook Kim, Kwon, Je-Keun, Cho, Yun-Ho, Kim, Woo Kyung, Osborne, Timothy F, Horton, Jay D, Jun, Hee-Sook, Ahn, Yong-Ho, Ahn, Sung-Min, Cha, Ji-Young
• Format: Article
• Language: English
• Subjects: Adenoviruses; Analysis; Base Sequence; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism; Bayesian analysis; Binding Sites; Biochemistry; Biology; Cancer; Carbohydrates; Cell growth; Chromatin; Chromatin Immunoprecipitation; Conserved sequence; Databases, Genetic; Deoxyribonucleic acid; Diabetes; DNA; DNA - metabolism; E coli; Escherichia coli; Experiments; Fatty acids; Gene clusters; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene sequencing; Gene set enrichment analysis; Genes; Genetic Loci - genetics; Genome, Human - genetics; Genomes; Genomics; Glucose; Glucose - pharmacology; HEK293 Cells; Helix-loop-helix proteins; Helix-loop-helix proteins (basic); Hep G2 Cells; Hepatocellular carcinoma; Humans; Immunoprecipitation; Kinases; Knowledge representation; Leucine; Leucine zipper proteins; Lipogenesis; Lipogenesis - drug effects; Lipogenesis - genetics; Liver; Liver - drug effects; Liver - metabolism; Medical research; Medicine; Metabolism; Molecular biology; Molecular Sequence Data; Polymerase chain reaction; Protein binding; Protein Binding - drug effects; Proteins; Reproducibility of Results; Rodents; Science; Signal Transduction - drug effects; Signal Transduction - genetics; Sterols; Target recognition; Transcription factors; Variance analysis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0022544

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.