title: Integrated expression profiling and genome-wide analysis of ChREBP targets reveals the dual role for ChREBP in glucose-regulated gene expression.
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.
authors.affiliation: Department of Molecular Medicine, Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Incheon, Korea.
authors.forename: Yun-Seung
authors.initials: YS
authors.lastname: Jeong
authors.forename: Deokhoon
authors.initials: D
authors.lastname: Kim
authors.forename: Yong Seok
authors.initials: YS
authors.lastname: Lee
authors.forename: Ha-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jung-Youn
authors.initials: JY
authors.lastname: Han
authors.forename: Seung-Soon
authors.initials: SS
authors.lastname: Im
authors.forename: Hansook Kim
authors.initials: HK
authors.lastname: Chong
authors.forename: Je-Keun
authors.initials: JK
authors.lastname: Kwon
authors.forename: Yun-Ho
authors.initials: YH
authors.lastname: Cho
authors.forename: Woo Kyung
authors.initials: WK
authors.lastname: Kim
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Osborne
authors.forename: Jay D
authors.initials: JD
authors.lastname: Horton
authors.forename: Hee-Sook
authors.initials: HS
authors.lastname: Jun
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Ahn
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Ahn
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Cha
mesh_terms: D001483:Base Sequence; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D056426:Genetic Loci / Q000235:genetics; D015894:Genome, Human / Q000235:genetics*; D005947:Glucose / Q000494:pharmacology*; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; C116385:MLXIPL protein, human; D004247:DNA; D005947:Glucose