title: Glucocorticoid receptor ChIP-sequencing of subcutaneous fat reveals modulation of inflammatory pathways.
abstract: OBJECTIVE
  To identify glucocorticoid receptor (GR)-associated chromatin sequences and target genes in primary human abdominal subcutaneous fat.
  
  
  METHODS
  GR chromatin immunoprecipitation (ChIP)-sequencing (seq) methodology in subcutaneous human adipocytes treated ex vivo with dexamethasone (dex) was optimized to identify genome-wide dex-dependent GR-binding regions (GBRs). Gene expression analyses were performed in parallel ± dex treatment.
  
  
  RESULTS
  Fat was obtained from four female surgical patients without obesity with a median age of 50.5 years. ChIP-seq analysis revealed 219 dex-associated GBRs. Of these, 136 GBRs were located within 100 kb of the transcriptional start site and associated with 123 genes. Combining these data with dex-induced gene expression, 70 of the 123 putative direct target genes were significantly up- or downregulated following 4 hours of dex treatment. Gene expression analysis demonstrated that the top 10 pathways reflected regulation of cellular metabolism and inflammation. DEPTOR, an inhibitor of mTOR, was identified as a potential direct GR target gene.
  
  
  CONCLUSIONS
  This is the first report of genome-wide GR ChIP-seq and gene expression analysis in human fat. The results implicate regulation of key GR target genes that are involved in dampening inflammation and promoting cellular metabolism.
authors.affiliation: Department of Surgery, the University of Chicago, Chicago, Ilinois, USA.|Department of Medicine, the University of Chicago, Chicago, Illinois, USA.
authors.forename: Puneet
authors.initials: P
authors.lastname: Singh
authors.affiliation: Department of Medicine, the University of Chicago, Chicago, Illinois, USA.
authors.forename: Clifton O
authors.initials: CO
authors.lastname: Brock
authors.affiliation: Committee on Molecular Metabolism and Nutrition, Department of Medicine, the University of Chicago, Chicago, Ilinois, USA.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Volden
authors.affiliation: Center for Research Informatics, the University of Chicago, Chicago, Illinois, USA.
authors.forename: Kyle
authors.initials: K
authors.lastname: Hernandez
authors.affiliation: Department of Medicine, the University of Chicago, Chicago, Illinois, USA.
authors.forename: Maxwell
authors.initials: M
authors.lastname: Skor
authors.affiliation: Department of Public Health Sciences, the University of Chicago, Chicago, Illinois, USA.
authors.forename: Masha
authors.initials: M
authors.lastname: Kocherginsky
authors.affiliation: Department of Surgery, the University of Chicago, Chicago, Ilinois, USA.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Park
authors.affiliation: Department of Medicine, the University of Chicago, Chicago, Illinois, USA.|Committee on Molecular Metabolism and Nutrition, Department of Medicine, the University of Chicago, Chicago, Ilinois, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Brady
authors.affiliation: Department of Medicine, the University of Chicago, Chicago, Illinois, USA.|Committee on Molecular Metabolism and Nutrition, Department of Medicine, the University of Chicago, Chicago, Ilinois, USA.|Ben May Department for Cancer Research, the University of Chicago, Chicago, Illinois, USA.
authors.forename: Suzanne D
authors.initials: SD
authors.lastname: Conzen
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D000369:Aged, 80 and over; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011485:Protein Binding / Q000187:drug effects; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism*; D017422:Sequence Analysis, DNA / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D050151:Subcutaneous Fat / Q000187:drug effects / Q000378:metabolism*
chemical_list: D011965:Receptors, Glucocorticoid; D003907:Dexamethasone