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

Research output: Contribution to journalArticle

86 Scopus citations

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.

Original languageEnglish (US)
Article numbere22544
JournalPloS one
Volume6
Issue number7
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Jeong, Y. S., Kim, D., Lee, Y. S., Kim, H. J., Han, J. Y., Im, S. S., Chong, H. K., Kwon, J. K., Cho, Y. H., Kim, W. K., Osborne, T. F., Horton, J. D., Jun, H. S., Ahn, Y. H., Ahn, S. M., & Cha, J. Y. (2011). Integrated expression profiling and Genome-Wide analysis of ChREBP targets reveals the dual role for ChREBP in Glucose-Regulated gene expression. PloS one, 6(7), [e22544]. https://doi.org/10.1371/journal.pone.0022544