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Chromatin Modifications Associated with Diabetes

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Abstract

Accelerated rates of vascular complications are associated with diabetes mellitus. Environmental factors including hyperglycaemia contribute to the progression of diabetic complications. Epidemiological and experimental animal studies identified poor glycaemic control as a major contributor to the development of complications. These studies suggest that early exposure to hyperglycaemia can instigate the development of complications that present later in the progression of the disease, despite improved glycaemic control. Recent experiments reveal a striking commonality associated with gene-activating hyperglycaemic events and chromatin modification. The best characterised to date are associated with the chemical changes of amino-terminal tails of histone H3. Enzymes that write specified histone tail modifications are not well understood in models of hyperglycaemia and metabolic memory as well as human diabetes. The best-characterised enzyme is the lysine specific Set7 methyltransferase. The contribution of Set7 to the aetiology of diabetic complications may extend to other transcriptional events through methylation of non-histone substrates.

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Acknowledgments

The authors acknowledge grant and fellowship support from the Juvenile Diabetes Research Foundation International, the Diabetes Australia Research Trust, the National Health and Medical Research Council (NHMRC) and the National Heart Foundation of Australia. STK is supported by an Australian Postgraduate Award. AE-O is a senior research fellow supported by the NHMRC. This study is supported in part by the Victorian Government’s Operational Infrastructure Support Program.

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Authors and Affiliations

  1. Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, 3004, Australia

    Samuel T. Keating & Assam El-Osta

  2. Epigenomics Profiling Facility, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, 3004, Australia

    Assam El-Osta

  3. Department of Pathology, The University of Melbourne, Melbourne, VIC, 3010, Australia

    Assam El-Osta

  4. Faculty of Medicine, Monash University, Melbourne, VIC, 3800, Australia

    Assam El-Osta

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  1. Samuel T. Keating
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  2. Assam El-Osta
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Correspondence to Assam El-Osta.

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Keating, S.T., El-Osta, A. Chromatin Modifications Associated with Diabetes. J. of Cardiovasc. Trans. Res. 5, 399–412 (2012). https://doi.org/10.1007/s12265-012-9380-9

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