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Chromatin Switching and Gene Dynamics Associated with Type 2 Diabetes

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Environmental Epigenomics in Health and Disease

Part of the book series: Epigenetics and Human Health ((EHH))

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Abstract

Type 2 diabetes (T2DM) is a chronic disease with a rapidly increasing global burden. An early event in the disease is deregulation of glycaemic control resulting in periods of hyperglycaemia. Large-scale clinical studies have shown that complications resulting from this hyperglycaemia can be manifest long after glycaemic control has been restored (UKPDS, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group. Lancet 352:837–852, 1998; Chalmers J, Cooper ME, UKPDS and the legacy effect. N Engl J Med 359:1618–1620, 2008), a phenomenon known as the “legacy effect” (Holman RR et al., 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359:1577–1589, 2008). Such continued development of cardiovascular complications, which result from prior exposure to hyperglycaemia, has led to the proposal of a “metabolic memory” (Cooper ME, Metabolic memory: implications for diabetic vascular complications. Pediatr Diabetes 10:343–346, 2009). Such a hypothesis suggests that a transient exposure to hyperglycaemia results in persistent changes in gene expression that are not reversed merely by restoring glycaemic control. Support for early, persistent changes came from the Diabetes Control and Complications Trial (DCCT) which revealed that early glycaemic control in diabetic patients led to sustained benefits and better outcomes (Cooper ME, Metabolic memory: implications for diabetic vascular complications. Pediatr Diabetes 10:343–346, 2009), and it has recently been proposed that minimising early exposure to hyperglycaemia is paramount (Aizawa T, Funase Y, Intervention at the very early stage of type 2 diabetes. Diabetologia 54:703–704; author reply 707–708, 2011). Currently, the most attractive potential mechanism responsible for the “legacy effect” is epigenetic, manifested by changes in DNA methylation and/or posttranslational modifications on histones. Over the last decade, numerous studies have identified correlations of specific epigenetic marks with type 2 diabetes, and more recently the mechanisms by which these changes lead to persistent alterations in gene expression levels have been interrogated.

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Abbreviations

CBP:

CREB-binding protein

COMPASS:

Complex proteins associated with Set1

CREB:

cAMP response element binding protein

DCCT:

Diabetes Control and Complications Trial

DNMT:

DNA methyltransferase

H3K4me1:

Monomethylated Histone H3 lysine 4

H3K4me2:

Dimethylated histone H3 lysine 4

H3K4me3:

Trimethyl histone H3 lysine 4

H3K9me2:

Dimethyl histone H3 lysine 9

HDAC:

Histone deacetylase

HAT:

Histone acetyltransferase

HMT:

Histone methyltransferase

HUVECS:

Human umbilical vein endothelial cells

IL:

Interleukin

JMJD2:

Jumonji domain 2

LSD1:

Lysine-specific demethylase 1

NFAT:

Nuclear factor of activated T cell

PGC-1α:

Peroxisome proliferator-activated receptor gamma coactivator-1 alpha

SAM:

S-adenosylmethionine

shRNA:

Short hairpin RNA

T2DM:

Type 2 diabetes mellitus

TGF:

Transforming growth factor

TNF:

Tumour necrosis factor

VEGF:

Vascular endothelial growth factor

VSMC:

Vascular smooth muscle cell

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Authors and Affiliations

  1. School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Garstang Building, Leeds, LS2 9JT, UK

    Ian C. Wood

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  1. Ian C. Wood
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Correspondence to Ian C. Wood .

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Editors and Affiliations

  1. , Department of Oncology, University of Wisconsin-Madison, University Avenue 1400, Madison, 53706, Wisconsin, USA

    Randy L. Jirtle

  2. National Institute of Environmental Hea, NIEHS, National Institutes of Health, Research Triangle Park, 27709, North Carolina, USA

    Frederick L. Tyson

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Wood, I.C. (2013). Chromatin Switching and Gene Dynamics Associated with Type 2 Diabetes. In: Jirtle, R., Tyson, F. (eds) Environmental Epigenomics in Health and Disease. Epigenetics and Human Health. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-36827-1_10

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