 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Aug 01, 2021 |
| Title |
Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci [RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Chromatin accessibility and gene expression in relevant cell contexts can guide identification of regulatory elements and mechanisms at genome-wide association study (GWAS) loci. To identify regulatory elements that display differential activity across adipocyte differentiation, we performed ATAC-seq and RNA-seq in a cell model of preadipocytes and adipocytes at days 4 and 14 of differentiation. For comparison, we created a consensus map of ATAC-seq peaks in 11 subcutaneous adipose tissue samples. A set of 15,919 adipocyte-dependent peaks showed stronger enrichment (60.1%) of adipocyte nuclei enhancers than 51,855 adipose tissue peaks (44.6%) or 18,244 preadipocyte-dependent peaks (11.5%). We linked context-dependent peaks to genes based on adipocyte promoter capture Hi-C data, overlap with adipose eQTL variants, and differential gene expression. Of 16,167 context-dependent peaks that could be linked to a gene, 5,184 were linked by two or more strategies to 1,675 genes. Among GWAS loci for cardiometabolic traits, adipocyte peaks showed the strongest enrichment for waist-to-hip ratio, coronary artery disease, and HDL-cholesterol, while adipose tissue peaks also showed significant enrichment for LDL-cholesterol and triglyceride levels. We identified 666 peaks linked to 507 genes by two or more methods and overlapping a GWAS signal, suggesting a regulatory mechanism at these loci. At one GWAS locus for palmitoleic acid, rs603424 was located in an adipocyte-dependent peak linked to SCD and exhibited allelic differences in transcriptional activity in adipocytes (P=0.003) but not preadipocytes (P=0.09). These results demonstrate that context-dependent peaks and genes can guide discovery of regulatory variants at GWAS loci and aid identification of regulatory mechanisms.
|
| |
|
| Overall design |
RNA-seq on SGBS preadipocytes and adipocytes at days 0, 2, 4, and 14 of differentiation
|
| |
|
| Contributor(s) |
Perrin HJ, Currin KW, Vadlamudi S, Pandey GK, Ng KK, Wabitsch M, Laakso M, Love MI, Mohlke KL |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Jun 23, 2021 |
| Last update date |
Aug 01, 2021 |
| Contact name |
Karen L Mohlke |
| E-mail(s) |
mohlke@med.unc.edu
|
| Organization name |
University of North Carolina at Chapel Hill
|
| Department |
Genetics
|
| Street address |
120 Mason Farm Road
|
| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599-7264 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
|
| Samples (18)
|
|
| This SubSeries is part of SuperSeries: |
| GSE178796 |
Chromatin accessibility and gene expression during adipocyte differentiation identify context-dependent effects at cardiometabolic GWAS loci |
|
| Relations |
| BioProject |
PRJNA740463 |
| SRA |
SRP325414 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE178795_DESeq2Datasets_forGEO_RNA_SGBS-days0-2-4-14.RData.gz |
14.9 Mb |
(ftp)(http) |
RDATA |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...