@article{Gaulton:2010:10.1038/ng.530,
author = {Gaulton, KJ and Nammo, T and Pasquali, L and Simon, JM and Giresi, PG and Fogarty, MP and Panhuis, TM and Mieczkowski, P and Secchi, A and Bosco, D and Berney, T and Montanya, E and Mohlke, KL and Lieb, JD and Ferrer, J},
doi = {10.1038/ng.530},
journal = {Nature Genetics},
pages = {255--U41},
title = {A map of open chromatin in human pancreatic islets},
url = {http://dx.doi.org/10.1038/ng.530},
volume = {42},
year = {2010}
}

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TY  - JOUR
AB  - Tissue-specific transcriptional regulation is central to human disease1. To identify regulatory DNA active in human pancreatic islets, we profiled chromatin by formaldehyde-assisted isolation of regulatory elements2,3,4 coupled with high-throughput sequencing (FAIRE-seq). We identified ∼80,000 open chromatin sites. Comparison of FAIRE-seq data from islets to that from five non-islet cell lines revealed ∼3,300 physically linked clusters of islet-selective open chromatin sites, which typically encompassed single genes that have islet-specific expression. We mapped sequence variants to open chromatin sites and found that rs7903146, a TCF7L2 intronic variant strongly associated with type 2 diabetes5, is located in islet-selective open chromatin. We found that human islet samples heterozygous for rs7903146 showed allelic imbalance in islet FAIRE signals and that the variant alters enhancer activity, indicating that genetic variation at this locus acts in cis with local chromatin and regulatory changes. These findings illuminate the tissue-specific organization of cis-regulatory elements and show that FAIRE-seq can guide the identification of regulatory variants underlying disease susceptibility.
AU  - Gaulton,KJ
AU  - Nammo,T
AU  - Pasquali,L
AU  - Simon,JM
AU  - Giresi,PG
AU  - Fogarty,MP
AU  - Panhuis,TM
AU  - Mieczkowski,P
AU  - Secchi,A
AU  - Bosco,D
AU  - Berney,T
AU  - Montanya,E
AU  - Mohlke,KL
AU  - Lieb,JD
AU  - Ferrer,J
DO  - 10.1038/ng.530
EP  - 41
PY  - 2010///
SN  - 1061-4036
SP  - 255
TI  - A map of open chromatin in human pancreatic islets
T2  - Nature Genetics
UR  - http://dx.doi.org/10.1038/ng.530
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000274912400016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.nature.com/articles/ng.530
UR  - http://hdl.handle.net/10044/1/79329
VL  - 42
ER  - 

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