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| Status |
Public on Apr 14, 2010 |
| Title |
Cell-Specific Determinants of PPARg Function in Adipocytes and Macrophages |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
The nuclear receptor Peroxisome Proliferator Activator Receptor (PPAR ) is the target of antidiabetic thiazolidinedione drugs, which improve insulin resistance but have side-effects that limit widespread use. PPAR is required for adipocyte differentiation, but is also expressed in other cell types, notably macrophages, where it influences atherosclerosis, insulin resistance, and inflammation. A central question is whether PPAR binding in macrophages occurs at the same or different genomic locations compared to adipocytes. Here, utilizing chromatin immunoprecipitation and high throughput sequencing (ChIP-seq), we demonstrate that PPAR cistromes in adipocytes and macrophages are predominantly cell type specific. In macrophages, PPAR 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. PPAR , when introduced into cells that are neither macrophages nor adipocytes, 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 PPAR function is regulated by cell-specific chromatin accessibility, histone marks, and transcription factors.
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| Overall design |
Genomic occupancy profiled by high throughput sequencing (ChIP-seq) from mouse macrophages for PPARgamma, PU.1, C/EBPbeta, H3K9Ace; and from 3T3-L1 adipocytes for PPARgamma and H3K9Ace
Masking file used to subtract input bias areas prior to generating final peak lists is linked below.
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| Contributor(s) |
Lefterova MI, Lazar MA |
| Citation(s) |
20176806 |
| Submission date |
Apr 12, 2010 |
| Last update date |
May 15, 2019 |
| Contact name |
Mitchell A. Lazar |
| E-mail(s) |
lazar@mail.med.upenn.edu
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| Organization name |
University of Pennsylvania
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| Department |
Institute for Diabetes, Obesity, and Metabolism
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| Lab |
Mitchell A. Lazar
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| Street address |
700 CRB, 415 Curie Blvd.
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| City |
philadelphia |
| State/province |
PA |
| ZIP/Postal code |
19104 |
| Country |
USA |
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| Platforms (1) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
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| Samples (6)
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| Relations |
| SRA |
SRP002300 |
| BioProject |
PRJNA126321 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE21314_Masking_file_Lefterova.bed.gz |
3.6 Kb |
(ftp)(http) |
BED |
| GSE21314_RAW.tar |
1.6 Mb |
(http)(custom) |
TAR (of BED, TXT) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
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