The Epigenome and Its Role in Diabetes
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GENETICS (T FRAYLING, SECTION EDITOR)
The Epigenome and Its Role in Diabetes Hironori Waki & Toshimasa Yamauchi & Takashi Kadowaki
Published online: 16 October 2012 # Springer Science+Business Media New York 2012
Abstract Both genetic and environmental factors play critical roles in the development of diabetes. Epidemiological evidence and data from clinical studies suggest the persistence of a “metabolic memory” of past exposures to environmental factors or glycemic control. Epigenetic mechanisms are regarded as one of the likeliest candidates underlying these phenomena. On the other hand, owing to the recent elucidation of mechanisms that erase epigenetic marks, it has gradually become recognized that epigenetic regulation is a more dynamic process than previously thought. A technological breakthrough in epigenome research in the past decade was the development of high-throughput sequencing. This new technology lets us investigate the epigenome in a global and comprehensive manner, and provides previously unrecognized findings and insights. This review presents an overview of the recent progress in our understanding of epigenetic regulation in type 1 and type 2 diabetes research. Keywords Epigenetics . Epigenomics . Epigenome . Next generation sequencer . High throughput sequencing . ChIPseq . FAIRE-seq . Histone methylation . Histone acetylation . DNA methylation . Diabetes . Metabolic memory . Legacy effect . Adipocytes . Pancreatic islet . Liver . Muscle . Vascular cells H. Waki : T. Yamauchi : T. Kadowaki (*) Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo, Tokyo 113-8655, Japan e-mail: [email protected] H. Waki Functional Regulation of Adipocytes, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo Bunkyo, Tokyo 113-8655, Japan
Introduction Genomic DNA in eukaryotes is tightly packed in the nucleus of the cell in combination with histone proteins, forming a highly-organized structure called “chromatin.” Regulation of chromatin structure is critical in transcriptional regulation of gene expression. Posttranslational modification of the chromatin such as DNA methylation, histone acetylation, and methylation is known to be an essential component of epigenetic regulation. There is an increasing awareness that epigenetic processes play a critical role in diabetes and metabolic disorders. Here, we review the definition of epigenetics and epigenomics with an emphasis on both stable and dynamic nature of epigenetics. We then discuss their role as a link between environmental factors and the development of diabetes, plus new findings and emerging concepts from genome-wide epigenomics analyses and recent advances in our understanding of epigenetic regulation in various organs related to diabetes; finally, we review the potential of epigenetic regulation as a target of drug development for the treatment of diabetes.
Epigenetics and Epigenomics In the 1940s, Conrad Waddington first created the term “epigenetics,” which wa
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