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Series GSE64458 Query DataSets for GSE64458
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
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.
 
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
 
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
Submission date Dec 23, 2014
Last update date May 15, 2019
Contact name Mitchell Lazar
E-mail(s) lazar@mail.med.upenn.edu
Organization name University of Pennsylvania
Lab Lazar Lab
Street address 3400 Civic Center Boulevard
City Philadelphia
State/province PA
ZIP/Postal code 19104
Country USA
 
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (37)
GSM1571705 B6_eWAT_12wLFD_2b
GSM1571706 B6_eWAT_12wLFD_3b
GSM1571707 129_eWAT_12wLFD_1
This SubSeries is part of SuperSeries:
GSE64460 Genetic Variation Determines PPARγ Function and Antidiabetic Drug Response In Vivo
Relations
BioProject PRJNA271059
SRA SRP051499

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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 SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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