A map of open chromatin in human pancreatic islets.

Nature Genetics
Kyle J GaultonJorge Ferrer

Abstract

Tissue-specific transcriptional regulation is central to human disease. To identify regulatory DNA active in human pancreatic islets, we profiled chromatin by formaldehyde-assisted isolation of regulatory elements coupled with high-throughput sequencing (FAIRE-seq). We identified approximately 80,000 open chromatin sites. Comparison of FAIRE-seq data from islets to that from five non-islet cell lines revealed approximately 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 diabetes, 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.

References

Apr 1, 1988·Transplantation·Z A LatifR Alejandro
Mar 1, 1994·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·L L WallrathS C Elgin
Dec 11, 1999·Nucleic Acids Research·E WingenderF Schacherer
Nov 22, 2001·Proceedings of the National Academy of Sciences of the United States of America·S F BojJ Ferrer
May 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Peter L NagyJason D Lieb
Sep 4, 2003·Genome Research·Paul D ThomasApurva Narechania
Dec 19, 2003·Nucleic Acids Research·Albin SandelinBoris Lenhard
Jan 1, 2004·Molecular Endocrinology·Kevin GerrishRoland Stein
Feb 28, 2004·Nucleic Acids Research·Martin C FrithZhiping Weng
Feb 28, 2004·Science·Duncan T OdomRichard A Young
Apr 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Andrew I SuJohn B Hogenesch
Sep 20, 2005·Genome Research·Belinda GiardineAnton Nekrutenko
Nov 10, 2005·Genome Biology·Michael J BuckJason D Lieb
Jan 18, 2006·Nature Genetics·Struan F A GrantKari Stefansson
Mar 1, 2006·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Niall Dillon
Sep 28, 2006·PLoS Genetics·Gregory J HoganJason D Lieb
Jan 9, 2007·Nature Genetics·Agnar HelgasonKári Stefánsson
Jul 3, 2007·Nature Genetics·Manjinder S SandhuInês Barroso
Nov 7, 2007·Genome Research·Webb MillerW James Kent
Nov 13, 2007·Trends in Pharmacological Sciences·Mark I McCarthy, Eleftheria Zeggini
Dec 7, 2007·Nature Reviews. Genetics·Steven Henikoff
Jun 6, 2008·PLoS Biology·Carol A EdwardsAnne C Ferguson-Smith
Aug 5, 2008·Genes & Development·Jennifer M Oliver-Krasinski, Doris A Stoffers
Aug 20, 2008·Nature Genetics·Kazuki YasudaMasato Kasuga
Sep 12, 2008·Bioinformatics·Alan P BoyleTerrence S Furey
Oct 15, 2008·Human Molecular Genetics·Karen L MohlkeGonçalo R Abecasis
Nov 20, 2008·Bioinformatics·Xiaohui XiePierre Baldi

❮ Previous
Next ❯

Citations

Nov 17, 2010·Cellular and Molecular Life Sciences : CMLS·Vivek S Chopra
Jan 14, 2012·Cellular and Molecular Life Sciences : CMLS·Nuria C Bramswig, Klaus H Kaestner
Sep 27, 2012·Diabetologia·D SavicM A Nobrega
Dec 15, 2012·Diabetologia·B R TennantB G Hoffman
Jun 8, 2011·Human Genetics·Mary E Travers, Mark I McCarthy
Jun 17, 2011·Clinical and Experimental Medicine·Abbasali PalizbanMohammad-Reza Maracy
Sep 30, 2010·Current Diabetes Reports·Martijn van de Bunt, Anna L Gloyn
Sep 18, 2012·Current Diabetes Reports·Karen L Mohlke, Laura J Scott
Sep 22, 2012·Current Diabetes Reports·Fiona McMurrayRoger D Cox
Oct 17, 2012·Current Diabetes Reports·Hironori WakiTakashi Kadowaki
Aug 3, 2013·Current Diabetes Reports·Cecile Haumaitre
Oct 16, 2013·Current Diabetes Reports·Hui Jin Ng, Anna L Gloyn
Apr 24, 2013·Journal of Applied Genetics·Uma GaurGuisheng Liu
Sep 1, 2011·Nature Methods·Monya Baker
Jun 10, 2010·Nature Reviews. Genetics·R David HawkinsBing Ren
Jun 19, 2012·Nature Reviews. Genetics·Ross C Hardison, James Taylor
Mar 2, 2011·The Pharmacogenomics Journal·C SunA Di Rienzo
Dec 15, 2010·The New England Journal of Medicine·Mark I McCarthy
Dec 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jiyoung ParkPhilipp E Scherer
Sep 7, 2012·The Journal of Biological Chemistry·Gabriel E Zentner, Peter C Scacheri
Nov 11, 2010·Briefings in Functional Genomics·Christopher G Bell, Stephan Beck
May 12, 2010·Briefings in Bioinformatics·Mikael Huss
Feb 4, 2012·Bioinformatics·William K M LaiMichael J Buck
Sep 18, 2010·Human Molecular Genetics·Ewan BirneyVishwanath R Iyer
Nov 13, 2012·Nucleic Acids Research·Mandana ArbabRichard I Sherwood
Jan 1, 2013·Nucleic Acids Research·Dennis WangLorenz Wernisch
Jun 26, 2012·Nucleic Acids Research·Aurélien A SérandourGilles Salbert
May 8, 2013·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Alvaro Rada-IglesiasJoanna Wysocka
Jun 16, 2011·Genome Research·Daniel SavicMarcelo A Nobrega
Sep 8, 2012·Genome Research·John A Stamatoyannopoulos

❮ Previous
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Methods Mentioned

BETA
FAIRE-seq
FCS
Genotyping
PCR
transfection
Assay

Software Mentioned

DAVID
MotifMap
PANTHER
Mapping and Assembly with Qualities ( MAQ )
ImageJ
FAIRE
Galaxy
PeakSeq
Clover

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