Linked Life Data

20176806

Source:http://linkedlifedata.com/resource/pubmed/id/20176806

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-4-8
pubmed:abstractText
The nuclear receptor peroxisome proliferator activator receptor gamma (PPARgamma) is the target of antidiabetic thiazolidinedione drugs, which improve insulin resistance but have side effects that limit widespread use. PPARgamma is required for adipocyte differentiation, but it is also expressed in other cell types, notably macrophages, where it influences atherosclerosis, insulin resistance, and inflammation. A central question is whether PPARgamma binding in macrophages occurs at genomic locations the same as or different from those in adipocytes. Here, utilizing chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq), we demonstrate that PPARgamma cistromes in mouse adipocytes and macrophages are predominantly cell type specific. In thioglycolate-elicited macrophages, PPARgamma colocalizes with the hematopoietic transcription factor PU.1 in areas of open chromatin and histone acetylation, near a distinct set of immune genes in addition to a number of metabolic genes shared with adipocytes. In adipocytes, the macrophage-unique binding regions are marked with repressive histone modifications, typically associated with local chromatin compaction and gene silencing. PPARgamma, when introduced into preadipocytes, bound only to regions depleted of repressive histone modifications, where it increased DNA accessibility, enhanced histone acetylation, and induced gene expression. Thus, the cell specificity of PPARgamma function is regulated by cell-specific transcription factors, chromatin accessibility, and histone marks. Our data support the existence of an epigenomic hierarchy in which PPARgamma binding to cell-specific sites not marked by repressive marks opens chromatin and leads to local activation marks, including histone acetylation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1098-5549
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2078-89
pubmed:dateRevised
2011-4-5
pubmed:meshHeading
pubmed-meshheading:20176806-3T3-L1 Cells, pubmed-meshheading:20176806-Acetylation, pubmed-meshheading:20176806-Adipocytes, pubmed-meshheading:20176806-Animals, pubmed-meshheading:20176806-Base Sequence, pubmed-meshheading:20176806-Binding Sites, pubmed-meshheading:20176806-CCAAT-Enhancer-Binding Protein-beta, pubmed-meshheading:20176806-Chromatin, pubmed-meshheading:20176806-DNA, pubmed-meshheading:20176806-Histones, pubmed-meshheading:20176806-Macrophages, pubmed-meshheading:20176806-Male, pubmed-meshheading:20176806-Mice, pubmed-meshheading:20176806-Mice, Inbred C57BL, pubmed-meshheading:20176806-Molecular Sequence Data, pubmed-meshheading:20176806-Organ Specificity, pubmed-meshheading:20176806-PPAR gamma, pubmed-meshheading:20176806-Protein Binding, pubmed-meshheading:20176806-Protein Transport, pubmed-meshheading:20176806-Proto-Oncogene Proteins, pubmed-meshheading:20176806-Trans-Activators, pubmed-meshheading:20176806-Transcriptional Activation
pubmed:year
2010
pubmed:articleTitle
Cell-specific determinants of peroxisome proliferator-activated receptor gamma function in adipocytes and macrophages.
pubmed:affiliation
University of Pennsylvania School of Medicine, 700 CRB, 415 Curie Blvd., Philadelphia, PA 19104-6149, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural