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PARylation, DNA (De)methylation, and Diabetes

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Handbook of Nutrition, Diet, and Epigenetics

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Abstract

Diabetes and diabetic complications, autoimmunity and inflammatory diseases, have recently become the focus of epigenetic therapy, since with epigenetic drugs it is possible to reverse aberrant gene expression profiles associated with the disease states. For diabetes, the therapy challenges depend on identifying the most appropriate molecular target and its influence on a relevant gene product. This chapter summarizes the current view on the interplay between ten-eleven translocation (TETs) and the poly(ADP-ribose) polymerase (PARPs) family of enzymes in regulating DNA methylation and how this interplay could be targeted to attenuate diabetes. This molecular interchange jigsaw puzzle is emerging as an important focus of research, and we can expect to see further advances in the elucidation of its role in diabetes as well as other pathologies. Moreover, the possibility for designating specific PARP-1 inhibitors as potential “EPI-drugs” for diabetes prevention/attenuation is also discussed. Understanding the epigenetic machinery and the differential roles of its components is essential for the development of targeted epigenetic therapies for diseases.

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Abbreviations

3AB:

3-aminobenzamide

5caC:

5-carboxylcytosine

5fC:

5-formylcytosine

5hmC:

5-hydroxymethylcytosine

5hmU:

5-hydroxymethyluridine

5mC:

5-methylcytosine

BER:

base excision repair

C:

cytosine

CpG:

cytosine-phosphate-guanine

CRISPR/Cas9:

clustered regularly interspaced short palindromic repeats/associated protein-9 nuclease

DNMTs:

DNA methyltransferases

NAD+:

nicotinamide adenine dinucleotide

PARPs:

poly(ADP-ribose) polymerase family of enzymes

PARs:

poly(ADP-ribose) polymers

PARylation:

poly(ADP-ribosyl)ation

PARG:

poly(ADP-ribose) glycohydrolases

RO/NS:

reactive oxygen/nitrogen species

T1D:

type 1 diabetes

T2D:

type 2 diabetes

TDG:

thymine-DNA glycosylase

TETs:

ten-eleven translocation family of enzymes

α-KG:

α-ketoglutarate

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Acknowledgments

This work was supported by the Alexander von Humboldt foundation, program for funding a Research Group Linkage (2014) and Ministry of Education, Science and Technological Development of the Republic of Serbia, Grant No. 173020. This article is based upon work from COST Action (CM1406), supported by COST (European Cooperation in Science and Technology), participants MV and TPJ.

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Authors and Affiliations

  1. Institute for Biological Research, University of Belgrade, Belgrade, Serbia

    Anja Tolić & Nevena Grdović

  2. Institute of Biochemistry, University of Stuttgart, Stuttgart, Germany

    Mirunalini Ravichandran & Tomasz P. Jurkowski

  3. Department of Molecular Biology, Institute for Biological Research Siniša Stanković, University of Belgrade, Belgrade, Serbia

    Melita Vidaković

Authors
  1. Melita Vidaković
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  2. Anja Tolić
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  3. Nevena Grdović
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  4. Mirunalini Ravichandran
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  5. Tomasz P. Jurkowski
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Correspondence to Melita Vidaković .

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Editors and Affiliations

  1. School of Life Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. Diabetes and Nutritional Sciences Research Division, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Victor R. Preedy

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Vidaković, M., Tolić, A., Grdović, N., Ravichandran, M., Jurkowski, T.P. (2019). PARylation, DNA (De)methylation, and Diabetes. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-55530-0_55

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  • DOI: https://doi.org/10.1007/978-3-319-55530-0_55

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