|
| Status |
Public on Nov 08, 2013 |
| Title |
Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants (ChIP-seq) |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
Chromatin-based functional genomic analyses and genomewide association studies (GWASs) together implicate enhancers as critical elements influencing gene expression and risk for common diseases. Here, we performed systematic chromatin and transcriptome pro- filing in human pancreatic islets. Integrated analysis of islet data with those generated by the ENCODE project in nine cell types identified specific and significant enrichment of type 2 diabetes and related quantitative trait GWAS variants in islet enhancers. Our integrated chromatin maps reveal that most enhancers are short (median = 0.8 kb). Each cell type also contains a substantial number of more extended (≥3 kb) enhancers. Interestingly, these stretch enhancers are often tissue-specific and overlap locus control regions, suggesting that they are important chromatin regulatory beacons. Indeed, we show that (i) tissue specificity of enhancers and nearby gene expression increase with enhancer length; (ii) neighborhoods containing stretch enhancers are enriched for important cell type– specific genes; and (iii) GWAS variants associated with traits rele- vant to a particular cell type are more enriched in stretch enhancers compared with short enhancers. Reporter constructs containing stretch enhancer sequences exhibited tissue-specific activity in cell culture experiments and in transgenic mice. These results suggest that stretch enhancers are critical chromatin elements for coordinating cell type–specific regulatory programs and that sequence variation in stretch enhancers affects risk of major common human diseases.
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| |
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| Overall design |
Integrated analysis of islet chromatin modification and transcriptome data with those generated by the ENCODE project.
NISC Comparative Sequencing Program
|
| Web link |
http://research.nhgri.nih.gov/manuscripts/Collins/islet_chromatin
|
| |
|
| Contributor(s) |
Parker SC, Stitzel ML, Taylor DL, Orozco JM, Erdos MR, Akiyama JA, van Bueren KL, Chines PS, Narisu N, Black BL, Visel A, Pennacchio LA, Collins FS |
| Citation(s) |
24127591 |
| |
| Submission date |
Sep 30, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Francis S Collins |
| E-mail(s) |
collinsf@mail.nih.gov
|
| Organization name |
NHGRI
|
| Department |
Genome Technology Branch
|
| Lab |
Molecular Genetics Section
|
| Street address |
1 Center Drive, Rm 126
|
| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
|
| Samples (9)
|
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| This SubSeries is part of SuperSeries: |
| GSE51312 |
Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants |
|
| Relations |
| BioProject |
PRJNA227219 |
| SRA |
SRP032815 |
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