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Profiling of promoter occupancy by PPARa in human hepatoma cells via ChIP-chip analysis
- Source :
- Nucleic acids research 38 (2010) 9, Nucleic Acids Research, Nucleic acids research, 38(9), 2839-2850
- Publication Year :
- 2010
-
Abstract
- The transcription factor peroxisome proliferator-activated receptor alpha (PPARalpha) is an important regulator of hepatic lipid metabolism. While PPARalpha is known to activate transcription of numerous genes, no comprehensive picture of PPARalpha binding to endogenous genes has yet been reported. To fill this gap, we performed Chromatin immunoprecipitation (ChIP)-chip in combination with transcriptional profiling on HepG2 human hepatoma cells treated with the PPARalpha agonist GW7647. We found that GW7647 increased PPARalpha binding to 4220 binding regions. GW7647-induced binding regions showed a bias around the transcription start site and most contained a predicted PPAR binding motif. Several genes known to be regulated by PPARalpha, such as ACOX1, SULT2A1, ACADL, CD36, IGFBP1 and G0S2, showed GW7647-induced PPARalpha binding to their promoter. A GW7647-induced PPARalpha-binding region was also assigned to SREBP-targets HMGCS1, HMGCR, FDFT1, SC4MOL, and LPIN1, expression of which was induced by GW7647, suggesting cross-talk between PPARalpha and SREBP signaling. Our data furthermore demonstrate interaction between PPARalpha and STAT transcription factors in PPARalpha-mediated transcriptional repression, and suggest interaction between PPARalpha and TBP, and PPARalpha and C/EBPalpha in PPARalpha-mediated transcriptional activation. Overall, our analysis leads to important new insights into the mechanisms and impact of transcriptional regulation by PPARalpha in human liver and highlight the importance of cross-talk with other transcription factors.
- Subjects :
- response element
Response element
Peroxisome proliferator-activated receptor
nuclear receptors
Biochemistry
Voeding, Metabolisme en Genomica
Transcriptional regulation
Cluster Analysis
peroxisome
Promoter Regions, Genetic
transcription factor
Oligonucleotide Array Sequence Analysis
chemistry.chemical_classification
Regulation of gene expression
Liver Neoplasms
food and beverages
Metabolism and Genomics
Metabolisme en Genomica
cardiovascular system
Nutrition, Metabolism and Genomics
lipids (amino acids, peptides, and proteins)
Transcription Initiation Site
Chromatin Immunoprecipitation
Carcinoma, Hepatocellular
Biochemie
Biology
Gene Regulation, Chromatin and Epigenetics
digestive system
Voeding
c-myc
proliferator-activated receptors
Cell Line, Tumor
Genetics
lipid-synthesis
Humans
PPAR alpha
Transcription factor
VLAG
Nutrition
Binding Sites
Gene Expression Profiling
nutritional and metabolic diseases
Molecular biology
Sterol regulatory element-binding protein
Nuclear receptor
chemistry
Gene Expression Regulation
primary target genes
factor-binding sites
gamma
Chromatin immunoprecipitation
Subjects
Details
- Language :
- English
- ISSN :
- 03051048
- Database :
- OpenAIRE
- Journal :
- Nucleic acids research 38 (2010) 9, Nucleic Acids Research, Nucleic acids research, 38(9), 2839-2850
- Accession number :
- edsair.doi.dedup.....13dc4babbf3f1d15bb47ea6893dc7c90