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Status |
Public on Jul 02, 2015 |
Title |
Genetic Variation Determines PPARγ Function and Antidiabetic Drug Response In Vivo [ChIP-seq] |
Organisms |
Homo sapiens; Mus musculus |
Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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Summary |
SNPs affecting disease risk often reside in non-coding genomic regions. Here we show that SNPs are highly enriched at mouse strain-selective adipose tissue binding sites for PPARγ, a nuclear receptor for antidiabetic drugs. Many such SNPs alter binding motifs for PPARγ or cooperating factors, and functionally regulate nearby genes whose expression is strain-selective and imbalanced in heterozygous F1 mice. Moreover, genetically-determined binding of PPARγ accounts for mouse strain-specific transcriptional effects of TZD drugs, providing proof-of- concept for personalized medicine related to nuclear receptor genomic occupancy. In human fat, motif-altering SNPs cause differential PPARγ binding, provide a molecular mechanism for some expression quantitative trait loci, and are risk factors for dysmetabolic traits in genome- wide association studies. One PPARγ motif-altering SNP is associated with HDL levels and other metabolic syndrome parameters. Thus, natural genetic variation in PPARγ genomic occupancy determines individual disease risk and drug response.
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Overall design |
6 ChIP-seq experiments conducted in mice and 5 in human subjects. Deep sequencing carried out using Illumina HiSeq2000 and the Solexa Analysis Pipeline eWAT; epididymal White Adipose Tissue iWAT; inguinal White Adipose Tissue 12wLFD; mice were fed a control low fat diet (Research Diet D12450B) chow; mice were fed standard rodent chow Diet GR; Glucocorticoid receptor
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Contributor(s) |
Soccio R, Chen ER, Rajapurkar SR, Safabakhsh P, Marinis JM, Dispirito JR, Emmett MJ, Briggs ER, Fang B, Everett LJ, Lim H, Won KJ, Steger DJ, Wu Y, Civelek M, Voight BF, Lazar M |
Citation(s) |
26140591 |
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Submission date |
Dec 23, 2014 |
Last update date |
May 15, 2019 |
Contact name |
Mitchell Lazar |
E-mail(s) |
lazar@mail.med.upenn.edu
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Organization name |
University of Pennsylvania
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Lab |
Lazar Lab
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Street address |
3400 Civic Center Boulevard
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City |
Philadelphia |
State/province |
PA |
ZIP/Postal code |
19104 |
Country |
USA |
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Platforms (2) |
GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
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Samples (37)
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This SubSeries is part of SuperSeries: |
GSE64460 |
Genetic Variation Determines PPARγ Function and Antidiabetic Drug Response In Vivo |
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Relations |
BioProject |
PRJNA271059 |
SRA |
SRP051499 |
Supplementary file |
Size |
Download |
File type/resource |
GSE64458_114S_all3.ucsc.bedGraph.gz |
51.2 Mb |
(ftp)(http) |
BEDGRAPH |
GSE64458_120S_all3.ucsc.bedGraph.gz |
50.9 Mb |
(ftp)(http) |
BEDGRAPH |
GSE64458_124S_all3.ucsc.bedGraph.gz |
49.4 Mb |
(ftp)(http) |
BEDGRAPH |
GSE64458_125S_all3.ucsc.bedGraph.gz |
50.4 Mb |
(ftp)(http) |
BEDGRAPH |
GSE64458_129_eWAT_12wLFD_12_gsnap.ucsc.bedGraph.gz |
41.9 Mb |
(ftp)(http) |
BEDGRAPH |
GSE64458_129_eWAT_chow_ab_gsnap.ucsc.bedGraph.gz |
39.0 Mb |
(ftp)(http) |
BEDGRAPH |
GSE64458_47893_all4.ucsc.bedGraph.gz |
49.5 Mb |
(ftp)(http) |
BEDGRAPH |
GSE64458_B6_eWAT_12wLFD_2b3b_gsnap.ucsc.bedGraph.gz |
41.7 Mb |
(ftp)(http) |
BEDGRAPH |
GSE64458_B6_eWAT_chow_ab_gsnap.ucsc.bedGraph.gz |
45.8 Mb |
(ftp)(http) |
BEDGRAPH |
GSE64458_F1_eWAT_chow_ab_gsnap.ucsc.bedGraph.gz |
38.5 Mb |
(ftp)(http) |
BEDGRAPH |
GSE64458_RAW.tar |
341.0 Mb |
(http)(custom) |
TAR (of BEDGRAPH) |
GSE64458_peakfile_universe_GR_80944.bed.gz |
1.2 Mb |
(ftp)(http) |
BED |
GSE64458_peakfile_universe_HAR_62188.bed.gz |
566.1 Kb |
(ftp)(http) |
BED |
GSE64458_peakfile_universe_PPARG_35226.bed.gz |
421.1 Kb |
(ftp)(http) |
BED |
SRA Run Selector |
Raw data are available in SRA |
Processed data provided as supplementary file |
Processed data are available on Series record |