Chromatin modifications associated with diabetes.
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.
Epigenetics in Human Health and Disease Laboratory, Baker IDI Heart and Diabetes Institute, The Alfred Medical Research and Education Precinct, Melbourne, VIC, Australia.
Samuel T
ST
Keating
Assam
A
El-Osta
D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D048909:Diabetes Complications / Q000097:blood / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D018450:Disease Progression; D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors
D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D011495:Histone-Lysine N-Methyltransferase; D006657:Histones; C517652:hemoglobin A1c protein, human; C540312:SETD7 protein, human