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| Status |
Public on Jun 30, 2011 |
| Title |
Identification and analysis of pancreatic islet specific enhancers |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
We anticipated that the identification of cis-regulatory regions active in pancreatic islets would help increase our understanding of islet biology and the pathology of diabetes. Towards this end we used histone H3 lysine 4 monomethylation-based nucleosome predictions genome-wide, in conjunction with binding data for PDX1, FOXA2, MAFA, and NEUROD1, to identify 3,654 putative enhancers that are H3K4me1-enriched uniquely in islets as compared to 14 other tissue or cell-types. We show that these islet-specific enhancers are associated with genes with significantly higher islet specificity than genes associated with non-specific enhancers. Further, islet-specific enhancers were not enriched for typical active or repressive histone methylations in embryonic stem cells and liver, suggesting they are formed by de novo histone methylation during pancreas development. We also identify a subset of enhancers bivalently marked by both H3K4me1 and H3K27me3 in adult pancreatic islets. Further, we show that islet-specific enhancers triple- or quadruple- bound by PDX1, MAFA, NEUROD1 and/or FOXA2 are associated with genes with particularly high islet-specificity, and that these loci are enriched in regions with functional activity in islet cell types. Finally, we demonstrate that cytokines reduce H3K4me1 enrichment levels at selected triple- or quadruple-bound islet-specific enhancers, suggesting that epigenetic changes may contribute to cytokine-induced b-cell dysfunction.
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| Overall design |
In conjunction with data from Hoffman et al Genome Research 2010, an analysis of histone modifications and transcription factor binding sites to identify enhancer regions
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| Contributor(s) |
Hoffman BG, Hoodless PA, Jones SJ |
| Citation(s) |
23238790 |
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| Submission date |
Jun 29, 2011 |
| Last update date |
May 15, 2019 |
| Contact name |
Patrick Plettner |
| E-mail(s) |
pplettner@bcgsc.ca
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| Organization name |
BC Cancer Agency GSC
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| Street address |
100-570 West 7th Avenue
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| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V5Z 4S6 |
| Country |
Canada |
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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 |
SRP007387 |
| BioProject |
PRJNA143799 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE30298_RAW.tar |
16.6 Gb |
(http)(custom) |
TAR (of BAM, TXT, WIG) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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