Analysis of the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) cistrome reveals novel co-regulatory role of ATF4

Combiz Khozoie, Michael G. Borland, Bokai Zhu, Songjoon Baek, Sam John, Gordon L. Hager, Yatrik M. Shah, Frank J. Gonzalez, Jeffrey M. Peters

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Background: The present study coupled expression profiling with chromatin immunoprecipitation sequencing (ChIP-seq) to examine peroxisome proliferator-activated receptor-β/δ (PPARβ/δ)-dependent regulation of gene expression in mouse keratinocytes, a cell type that expresses PPARβ/δ in high concentration.Results: Microarray analysis elucidated eight different types of regulation that modulated PPARβ/δ-dependent gene expression of 612 genes ranging from repression or activation without an exogenous ligand, repression or activation with an exogenous ligand, or a combination of these effects. Bioinformatic analysis of ChIP-seq data demonstrated promoter occupancy of PPARβ/δ for some of these genes, and also identified the presence of other transcription factor binding sites in close proximity to PPARβ/δ bound to chromatin. For some types of regulation, ATF4 is required for ligand-dependent induction of PPARβ/δ target genes.Conclusions: PPARβ/δ regulates constitutive expression of genes in keratinocytes, thus suggesting the presence of one or more endogenous ligands. The diversity in the types of gene regulation carried out by PPARβ/δ is consistent with dynamic binding and interactions with chromatin and indicates the presence of complex regulatory networks in cells expressing high levels of this nuclear receptor such as keratinocytes. Results from these studies are the first to demonstrate that differences in DNA binding of other transcription factors can directly influence the transcriptional activity of PPARβ/δ.

Original languageEnglish (US)
Article number665
JournalBMC genomics
Volume13
Issue number1
DOIs
StatePublished - Nov 24 2012

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Peroxisome Proliferator-Activated Receptors
Keratinocytes
Ligands
Chromatin Immunoprecipitation
Genes
Chromatin
Transcription Factors
Gene Expression
Gene Expression Regulation
Microarray Analysis
Cytoplasmic and Nuclear Receptors
Computational Biology
Binding Sites
DNA

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Genetics

Cite this

Khozoie, Combiz ; Borland, Michael G. ; Zhu, Bokai ; Baek, Songjoon ; John, Sam ; Hager, Gordon L. ; Shah, Yatrik M. ; Gonzalez, Frank J. ; Peters, Jeffrey M. / Analysis of the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) cistrome reveals novel co-regulatory role of ATF4. In: BMC genomics. 2012 ; Vol. 13, No. 1.
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abstract = "Background: The present study coupled expression profiling with chromatin immunoprecipitation sequencing (ChIP-seq) to examine peroxisome proliferator-activated receptor-β/δ (PPARβ/δ)-dependent regulation of gene expression in mouse keratinocytes, a cell type that expresses PPARβ/δ in high concentration.Results: Microarray analysis elucidated eight different types of regulation that modulated PPARβ/δ-dependent gene expression of 612 genes ranging from repression or activation without an exogenous ligand, repression or activation with an exogenous ligand, or a combination of these effects. Bioinformatic analysis of ChIP-seq data demonstrated promoter occupancy of PPARβ/δ for some of these genes, and also identified the presence of other transcription factor binding sites in close proximity to PPARβ/δ bound to chromatin. For some types of regulation, ATF4 is required for ligand-dependent induction of PPARβ/δ target genes.Conclusions: PPARβ/δ regulates constitutive expression of genes in keratinocytes, thus suggesting the presence of one or more endogenous ligands. The diversity in the types of gene regulation carried out by PPARβ/δ is consistent with dynamic binding and interactions with chromatin and indicates the presence of complex regulatory networks in cells expressing high levels of this nuclear receptor such as keratinocytes. Results from these studies are the first to demonstrate that differences in DNA binding of other transcription factors can directly influence the transcriptional activity of PPARβ/δ.",
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Analysis of the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) cistrome reveals novel co-regulatory role of ATF4. / Khozoie, Combiz; Borland, Michael G.; Zhu, Bokai; Baek, Songjoon; John, Sam; Hager, Gordon L.; Shah, Yatrik M.; Gonzalez, Frank J.; Peters, Jeffrey M.

In: BMC genomics, Vol. 13, No. 1, 665, 24.11.2012.

Research output: Contribution to journalArticle

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T1 - Analysis of the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) cistrome reveals novel co-regulatory role of ATF4

AU - Khozoie, Combiz

AU - Borland, Michael G.

AU - Zhu, Bokai

AU - Baek, Songjoon

AU - John, Sam

AU - Hager, Gordon L.

AU - Shah, Yatrik M.

AU - Gonzalez, Frank J.

AU - Peters, Jeffrey M.

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Y1 - 2012/11/24

N2 - Background: The present study coupled expression profiling with chromatin immunoprecipitation sequencing (ChIP-seq) to examine peroxisome proliferator-activated receptor-β/δ (PPARβ/δ)-dependent regulation of gene expression in mouse keratinocytes, a cell type that expresses PPARβ/δ in high concentration.Results: Microarray analysis elucidated eight different types of regulation that modulated PPARβ/δ-dependent gene expression of 612 genes ranging from repression or activation without an exogenous ligand, repression or activation with an exogenous ligand, or a combination of these effects. Bioinformatic analysis of ChIP-seq data demonstrated promoter occupancy of PPARβ/δ for some of these genes, and also identified the presence of other transcription factor binding sites in close proximity to PPARβ/δ bound to chromatin. For some types of regulation, ATF4 is required for ligand-dependent induction of PPARβ/δ target genes.Conclusions: PPARβ/δ regulates constitutive expression of genes in keratinocytes, thus suggesting the presence of one or more endogenous ligands. The diversity in the types of gene regulation carried out by PPARβ/δ is consistent with dynamic binding and interactions with chromatin and indicates the presence of complex regulatory networks in cells expressing high levels of this nuclear receptor such as keratinocytes. Results from these studies are the first to demonstrate that differences in DNA binding of other transcription factors can directly influence the transcriptional activity of PPARβ/δ.

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