title: Analysis of the peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) cistrome reveals novel co-regulatory role of ATF4.
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.
authors.affiliation: Department of Veterinary and Biomedical Sciences and The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Combiz
authors.initials: C
authors.lastname: Khozoie
authors.forename: Michael G
authors.initials: MG
authors.lastname: Borland
authors.forename: Bokai
authors.initials: B
authors.lastname: Zhu
authors.forename: Songjoon
authors.initials: S
authors.lastname: Baek
authors.forename: Sam
authors.initials: S
authors.lastname: John
authors.forename: Gordon L
authors.initials: GL
authors.lastname: Hager
authors.forename: Yatrik M
authors.initials: YM
authors.lastname: Shah
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Gonzalez
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Peters
mesh_terms: D051701:Activating Transcription Factor 4 / Q000737:chemistry / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D023281:Genomics; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D047494:PPAR delta / Q000235:genetics* / Q000378:metabolism*; D048068:PPAR-beta / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D047494:PPAR delta; D048068:PPAR-beta; D051701:Activating Transcription Factor 4; D004247:DNA