BibTex format
@article{Pasquali:2014:10.1038/ng.2870,
author = {Pasquali, L and Gaulton, KJ and Rodriguez-Segui, SA and Mularoni, L and Miguel-Escalada, I and Akerman, I and Tena, JJ and Moran, I and Gomez-Marin, C and van, de Bunt M and Ponsa-Cobas, J and Castro, N and Nammo, T and Cebola, I and Garcia-Hurtado, J and Angel, Maestro M and Pattou, F and Piemonti, L and Berney, T and Gloyn, AL and Ravassard, P and Luis, Gomez-Skarmeta J and Mueller, F and McCarthy, MI and Ferrer, J},
doi = {10.1038/ng.2870},
journal = {Nature Genetics},
pages = {136--+},
title = {Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants},
url = {http://dx.doi.org/10.1038/ng.2870},
volume = {46},
year = {2014}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Type 2 diabetes affects over 300 million people, causing severe complications and premature death, yet the underlying molecular mechanisms are largely unknown. Pancreatic islet dysfunction is central in type 2 diabetes pathogenesis, and understanding islet genome regulation could therefore provide valuable mechanistic insights. We have now mapped and examined the function of human islet cis-regulatory networks. We identify genomic sequences that are targeted by islet transcription factors to drive islet-specific gene activity and show that most such sequences reside in clusters of enhancers that form physical three-dimensional chromatin domains. We find that sequence variants associated with type 2 diabetes and fasting glycemia are enriched in these clustered islet enhancers and identify trait-associated variants that disrupt DNA binding and islet enhancer activity. Our studies illustrate how islet transcription factors interact functionally with the epigenome and provide systematic evidence that the dysregulation of islet enhancers is relevant to the mechanisms underlying type 2 diabetes.
AU - Pasquali,L
AU - Gaulton,KJ
AU - Rodriguez-Segui,SA
AU - Mularoni,L
AU - Miguel-Escalada,I
AU - Akerman,I
AU - Tena,JJ
AU - Moran,I
AU - Gomez-Marin,C
AU - van,de Bunt M
AU - Ponsa-Cobas,J
AU - Castro,N
AU - Nammo,T
AU - Cebola,I
AU - Garcia-Hurtado,J
AU - Angel,Maestro M
AU - Pattou,F
AU - Piemonti,L
AU - Berney,T
AU - Gloyn,AL
AU - Ravassard,P
AU - Luis,Gomez-Skarmeta J
AU - Mueller,F
AU - McCarthy,MI
AU - Ferrer,J
DO - 10.1038/ng.2870
EP - 136
PY - 2014///
SN - 1546-1718
SP - 136
TI - Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants
T2 - Nature Genetics
UR - http://dx.doi.org/10.1038/ng.2870
UR - http://hdl.handle.net/10044/1/24480
VL - 46
ER -
