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Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci.

Publication ,  Journal Article
Stitzel, ML; Sethupathy, P; Pearson, DS; Chines, PS; Song, L; Erdos, MR; Welch, R; Parker, SCJ; Boyle, AP; Scott, LJ; Margulies, EH; Furey, TS ...
Published in: Cell Metab
November 3, 2010

Identifying cis-regulatory elements is important to understanding how human pancreatic islets modulate gene expression in physiologic or pathophysiologic (e.g., diabetic) conditions. We conducted genome-wide analysis of DNase I hypersensitive sites, histone H3 lysine methylation modifications (K4me1, K4me3, K79me2), and CCCTC factor (CTCF) binding in human islets. This identified ∼18,000 putative promoters (several hundred unannotated and islet-active). Surprisingly, active promoter modifications were absent at genes encoding islet-specific hormones, suggesting a distinct regulatory mechanism. Of 34,039 distal (nonpromoter) regulatory elements, 47% are islet unique and 22% are CTCF bound. In the 18 type 2 diabetes (T2D)-associated loci, we identified 118 putative regulatory elements and confirmed enhancer activity for 12 of 33 tested. Among six regulatory elements harboring T2D-associated variants, two exhibit significant allele-specific differences in activity. These findings present a global snapshot of the human islet epigenome and should provide functional context for noncoding variants emerging from genetic studies of T2D and other islet disorders.

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

November 3, 2010

Volume

12

Issue

5

Start / End Page

443 / 455

Location

United States

Related Subject Headings

  • Repressor Proteins
  • Regulatory Sequences, Nucleic Acid
  • Promoter Regions, Genetic
  • Methylation
  • Lysine
  • Islets of Langerhans
  • Humans
  • Histones
  • Hela Cells
  • HeLa Cells
 

Citation

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Chicago
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Stitzel, M. L., Sethupathy, P., Pearson, D. S., Chines, P. S., Song, L., Erdos, M. R., … Collins, F. S. (2010). Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci. Cell Metab, 12(5), 443–455. https://doi.org/10.1016/j.cmet.2010.09.012
Stitzel, Michael L., Praveen Sethupathy, Daniel S. Pearson, Peter S. Chines, Lingyun Song, Michael R. Erdos, Ryan Welch, et al. “Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci.Cell Metab 12, no. 5 (November 3, 2010): 443–55. https://doi.org/10.1016/j.cmet.2010.09.012.
Stitzel ML, Sethupathy P, Pearson DS, Chines PS, Song L, Erdos MR, et al. Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci. Cell Metab. 2010 Nov 3;12(5):443–55.
Stitzel, Michael L., et al. “Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci.Cell Metab, vol. 12, no. 5, Nov. 2010, pp. 443–55. Pubmed, doi:10.1016/j.cmet.2010.09.012.
Stitzel ML, Sethupathy P, Pearson DS, Chines PS, Song L, Erdos MR, Welch R, Parker SCJ, Boyle AP, Scott LJ, NISC Comparative Sequencing Program, Margulies EH, Boehnke M, Furey TS, Crawford GE, Collins FS. Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci. Cell Metab. 2010 Nov 3;12(5):443–455.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

November 3, 2010

Volume

12

Issue

5

Start / End Page

443 / 455

Location

United States

Related Subject Headings

  • Repressor Proteins
  • Regulatory Sequences, Nucleic Acid
  • Promoter Regions, Genetic
  • Methylation
  • Lysine
  • Islets of Langerhans
  • Humans
  • Histones
  • Hela Cells
  • HeLa Cells