Pancreatic islet chromatin accessibility and conformation reveals distal enhancer networks of type 2 diabetes risk

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

2 Scopus Citations
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Author(s)

  • William W. Greenwald
  • Joshua Chiou
  • Yunjiang Qiu
  • Ning Dai
  • Allen Wang
  • Naoki Nariai
  • Anthony Aylward
  • Jee Yun Han
  • Nikita Kadakia
  • Laura Regue
  • Mei-Lin Okino
  • Frauke Drees
  • Dana Kramer
  • Nicholas Vinckier
  • Liliana Minichiello
  • David Gorkin
  • Joseph Avruch
  • Kelly A. Frazer
  • Maike Sander
  • Bing Ren
  • Kyle J. Gaulton

Detail(s)

Original languageEnglish
Article number2078
Number of pages12
Journal / PublicationNature Communications
Volume10
Online published7 May 2019
Publication statusPublished - 7 May 2019
Externally publishedYes

Link(s)

Abstract

Genetic variants affecting pancreatic islet enhancers are central to T2D risk, but the gene targets of islet enhancer activity are largely unknown. We generate a high-resolution map of islet chromatin loops using Hi-C assays in three islet samples and use loops to annotate target genes of islet enhancers defined using ATAC-seq and published ChIP-seq data. We identify candidate target genes for thousands of islet enhancers, and find that enhancer looping is correlated with islet-specific gene expression. We fine-map T2D risk variants affecting islet enhancers, and find that candidate target genes of these variants defined using chromatin looping and eQTL mapping are enriched in protein transport and secretion pathways. At IGF2BP2, a fine-mapped T2D variant reduces islet enhancer activity and IGF2BP2 expression, and conditional inactivation of IGF2BP2 in mouse islets impairs glucose-stimulated insulin secretion. Our findings provide a resource for studying islet enhancer function and identifying genes involved in T2D risk.

Research Area(s)

  • GENOME-WIDE ASSOCIATION, GENE-EXPRESSION, READ ALIGNMENT, ANNOTATION, DISCOVERY, CELL, SEQ, PROVIDES, ELEMENTS, SUITE

Citation Format(s)

Pancreatic islet chromatin accessibility and conformation reveals distal enhancer networks of type 2 diabetes risk. / Greenwald, William W.; Chiou, Joshua; Yan, Jian; Qiu, Yunjiang; Dai, Ning; Wang, Allen; Nariai, Naoki; Aylward, Anthony; Han, Jee Yun; Kadakia, Nikita; Regue, Laura; Okino, Mei-Lin; Drees, Frauke; Kramer, Dana; Vinckier, Nicholas; Minichiello, Liliana; Gorkin, David; Avruch, Joseph; Frazer, Kelly A.; Sander, Maike; Ren, Bing; Gaulton, Kyle J.

In: Nature Communications, Vol. 10, 2078, 07.05.2019.

Research output: Journal Publications and Reviews (RGC: 21, 22, 62)21_Publication in refereed journalNot applicablepeer-review

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