The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Distinguishing Hyperglycemic Changes by Set7 in Vascular Endothelial Cells
Open accessAbstract
Rationale: Epigenetic changes are implicated in the persisting vascular effects of hyperglycemia. The precise mechanism whereby chromatin structure and subsequent gene expression are regulated by glucose in vascular endothelial cells remain to be fully defined. Objective: We have studied the molecular and functional mechanism whereby the Set7 methyltransferase associates with chromatin formation and histone methylation in vascular cells in response to current and previous exposure to glucose. Methods and Results: To characterize the molecular and functional identity of the Set7 protein, we used vascular cells overexpressing or lacking Set7. Chromatin fractionation for mono-methylation of lysine 4 on histone H3 identified methyltransferase activity. Immunofluorescence experiments strongly suggest that Set7 protein accumulates in the nucleus in response to hyperglycemia. Moreover, activation of proinflammatory genes by high glucose is dependent on Set7 but distinguished by H3K4m1 gene patterns. We show that transient hyperglycemia regulates the expression of proinflammatory genes in vascular endothelial cells in vitro and the persistent increase in glucose-induced gene expression in the aorta of nondiabetic mice. Conclusions: This study uncovers that the response to hyperglycemia in vascular endothelial cells involves the H3K4 methyltransferase, Set7. This enzyme appears to regulate glucose-induced chromatin changes and gene expression not only by H3K4m1-dependent but also H3K4m1-independent pathways. Furthermore, Set7 appears to be responsible for sustained vascular gene expression in response to prior hyperglycemia and is a potential molecular mechanism for the phenomenon of hyperglycemic memory.
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“Whilst DNA methylation modifications are believed to confer ‘metabolic memory’ other studies indicate histone modifications regulate the expression of genes implicated in diabetic complications 98, 99.”
From The Circadian Syndrome: is the Metabolic Syndrome and much more! (2019) · cites this paper as [99]
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Thomas, M. C., Brownlee, M., Suszták, K., Sharma, K., Jandeleit-Dahm, K. A. M., Zoungas, S., Rossing, P. R., Groop, P., & Cooper, M. E. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.18 · Cited by 1,335
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Metadata
- Authors
- Okabe, J., Orlowski, C., Balcerczyk, A., Tikellis, C., Thomas, M. C., Cooper, M. E., & El-Osta, A.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- From the Epigenetics in Human Health and Disease Laboratory (J.O., C.O., A.B., A.E.-O.), Epigenomic Profiling Facility (A.E.-O.), JDRF Danielle Alberti Memorial Centre for Diabetic Complications (C.T., M.C.T., M.E.C., A.E.-O.), Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, Victoria, Australia; the Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia (A.E.-O.); and the Faculty of Medicine, Nursing, and Health...
- Venue
- Circulation Research
- Published
- 2012-04-13
- Volume
- 110
- Issue
- 8
- Pages
- 1067-1076
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2110617730
- Cited by
- 180
- References
- 47
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 9 · 2023: 10 · 2022: 13 · 2021: 12 · 2020: 10 · 2019: 12 · 2018: 9 · 2017: 14 · 2016: 11 · 2015: 22 · 2014: 15 · 2013: 19 · 2012: 4
- FWCI
- 7.71
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Juvenile Diabetes Research Foundation International
- Diabetes Australia Research Trust
- Diabetes Australia
- National Heart Foundation of Australia
- State Government of Victoria
- Medical Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Keywords
- SET7, histone methyltransferase, hyperglycemia, vascular endothelial cells, H3K4 methylation, chromatin structure, pro-inflammatory gene expression, aorta, epigenetic regulation
- MeSH terms
- Animals, Aorta, Cell Line, Cell Nucleus, Diabetic Angiopathies, Disease Models, Animal, Gene Expression Regulation, Glucose, Humans, Hyperglycemia, Inflammation, Male, Microscopy, Fluorescence, Histone-Lysine N-Methyltransferase, Protein Methyltransferases, Time Factors, Transfection, Inflammation Mediators, RNA Interference, Chromatin Assembly and Disassembly, Endothelial Cells, Chromatin Immunoprecipitation, Mice
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