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Genome-wide analysis of histone modifications in human pancreatic islets
Open accessAbstract
The global diabetes epidemic poses a major challenge. Epigenetic events contribute to the etiology of diabetes; however, the lack of epigenomic analysis has limited the elucidation of the mechanistic basis for this link. To determine the epigenetic architecture of human pancreatic islets we mapped the genome-wide locations of four histone marks: three associated with gene activation—H3K4me1, H3K4me2, and H3K4me3—and one associated with gene repression, H3K27me3. Interestingly, the promoters of the highly transcribed insulin and glucagon genes are occupied only sparsely by H3K4me2 and H3K4me3. Globally, we identified important relationships between promoter structure, histone modification, and gene expression. We demonstrated co-occurrences of histone modifications including bivalent marks in mature islets. Furthermore, we found a set of promoters that is differentially modified between islets and other cell types. We also use our histone marks to determine which of the known diabetes-associated single-nucleotide polymorphisms are likely to be part of regulatory elements. Our global map of histone marks will serve as an important resource for understanding the epigenetic basis of type 2 diabetes.
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“Studies of pancreatic islets from nondiabetic donors ( 19 , 20 ) and patients with T2D ( 21 ) have identified epigenetic modifications in genes that potentially affect β-cell function.”
From β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment (2014) · cites this paper as [19]
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Citations
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Epigenetics in Human Obesity and Type 2 Diabetes
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“Studies of pancreatic islets from nondiabetic donors (19,20) and patients with T2D (21) have identified epigenetic modifications in genes that potentially affect b-cell function.”
Background
Metadata
- Authors
- Bhandare, R., Schug, J., Le Lay, J., Fox, A., Smirnova, O., Liu, C., Naji, A., & Kaestner, K. H.
- Affiliations
- University of Pennsylvania (US)
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2010-02-24
- Volume
- 20
- Issue
- 4
- Pages
- 428-433
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC2847745
- OpenAlex
- W2149952464
- Cited by
- 136
- References
- 27
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 19 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 11 · 2016: 3 · 2015: 12 · 2014: 14 · 2013: 17 · 2012: 13
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 19525, DK R01-055342, R01DK055342, U01DK070430, P30DK019525)
- National Center for Research Resources (U42RR016600)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- histone modifications, pancreatic islets, type 2 diabetes, epigenetics, H3K4me1, H3K4me2, H3K4me3, H3K27me3, insulin gene, promoter structure, gene expression regulation, regulatory elements
- MeSH terms
- Histone Methyltransferases, Diabetes Mellitus, Type 2, Histones, Humans, Islets of Langerhans, Methylation, Promoter Regions, Genetic, Histone-Lysine N-Methyltransferase, Protein Processing, Post-Translational, Transcriptional Activation, CpG Islands, Polymorphism, Single Nucleotide, Gene Expression Profiling, Epigenesis, Genetic, Validation Studies as Topic, Genome-Wide Association Study
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