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

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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

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response elements
Response Elements
Gene expression
binding proteins
Carrier Proteins
Genes
Carbohydrates
Genome
carbohydrates
Gene Expression
Glucose
gene expression
glucose
genome
genes
protein binding
Protein Binding
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
chromatin
Chromatin

ASJC Scopus subject areas

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

Cite this

Integrated expression profiling and Genome-Wide analysis of ChREBP targets reveals the dual role for ChREBP in Glucose-Regulated gene expression. / 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.

In: PLoS One, Vol. 6, No. 7, e22544, 2011.

Research output: Contribution to journalArticle

Jeong, YS, Kim, D, Lee, YS, Kim, HJ, Han, JY, Im, SS, Chong, HK, Kwon, JK, Cho, YH, Kim, WK, Osborne, TF, Horton, JD, Jun, HS, Ahn, YH, Ahn, SM & Cha, JY 2011, 'Integrated expression profiling and Genome-Wide analysis of ChREBP targets reveals the dual role for ChREBP in Glucose-Regulated gene expression', PLoS One, vol. 6, no. 7, e22544. https://doi.org/10.1371/journal.pone.0022544
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. / Integrated expression profiling and Genome-Wide analysis of ChREBP targets reveals the dual role for ChREBP in Glucose-Regulated gene expression. In: PLoS One. 2011 ; Vol. 6, No. 7.
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