Open chromatin in human pancreatic islets (FAIRE-seq) - Study GBCO4075
Genomics Study Specifications
|Study Name||Open chromatin in human pancreatic islets (FAIRE-seq)|
|Contact Name||Kyle J. Gaulton (University of North Carolina at Chapel Hill)|
|My Strategies||Return to My Strategies page|
|Classification||Tissue expression, surveys and comparisons|
|BCBC Release Date||January 04, 2011|
|Public Release Date||January 04, 2011|
|Citation||Gaulton KJ, Nammo T, Pasquali L, Simon JM, Giresi PG, Fogarty MP, Panhuis TM, Mieczkowski P, Secchi A, Bosco D, Berney T, Montanya E, Mohlke KL, Lieb JD, Ferrer J. A map of open chromatin in human pancreatic islets. Nat Genet. 2010. 42:255-9|
The goal of this experiment was to identify active regulatory DNA in human pancreatic islets. This was accomplished using high-throughput sequencing of genomic regions isolated using FAIRE from three purified pancreatic islet samples. FAIRE-seq data were technically validated by comparing to gene expression patterns determined by hybridizing the FAIRE samples to a tiling DNA microarray. Comparison between islet and non-islet cell lines releaved ~3,300 physically linked clusters of open chromatin sites, many encompassing single genes with islet-specific expression. By mapping sequence variants to open chromatin sites, we were also able to identify an association between rs7903146, a TCF7L2 intronic variant, and type 2 diabetes.
Identify regulatory DNA active in human pancreatic islets.
Chromatin from human islets was profiled using formaldehyde-assisted isolation of regulatory elements coupled with high throughput sequencing (FAIRE-seq).
FAIRE-seq led to identification of about 80,000 regions of open chromatin in human islets. These were concordant with those found on the same samples using microarrays. Three islet samples reflecting different ages, cause of death, genotype, islet isolation procedures, and exocrine contamination shared the majority of regions detected by FAIRE-seq. Promoters bound by RNA PolII and HNF4A or HNF1A (Odom et al. Science 2004) were enriched by FAIRE more than other promoters. Comparison of islet FAIRE-seq data to that from 5 other non-islet cell lines revealed about 3,300 physically linked clusters of of islet-selective open chromatin sites typically encompassing single genes with islet-specific expression. Ubiquitous intergenic open chromatin coincided more often than expected by chance with CTCF binding sites. Islet-selective open chromatin preferentially harbors DNA motifs of pancreatic islet transcription factors. The sequence variant, rs7903146, located in a TCF7L2 intron and strongly associated with T2D is located in islet-selective open chromatin. T/C allelic imbalance at this variant alters FAIRE-seq signals in human islets (T associated with more open chromatin and T2D susceptibility) and enhancer activity (T associated with greater activity) in MIN6 and 832/13 cell lines.
FAIRE-seq detected loci of islet-selective open chromatin integral to islet cell biology and disease.
|Platform types||Open chromatin FAIRE-Seq, Epigenomic|
|Study Design Type||
|Study Factors||Show study factors|
|Study Assays||Show study assays|
Access to Study Data
This Study Data is publicly available to all users.
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Last modified on Aug 02, 2011
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