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PARylation, DNA (De)methylation, and Diabetes

  • Melita VidakovićEmail author
  • Anja Tolić
  • Nevena Grdović
  • Mirunalini Ravichandran
  • Tomasz P. Jurkowski
Reference work entry

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.

Keywords

Diabetes DNA methylation DNA demethylation DNMT enzymes Epigenetic drug targets Chromatin architecture PARylation PARP-1 inhibitors TET enzymes 

List of 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

Notes

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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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Melita Vidaković
    • 3
    Email author
  • Anja Tolić
    • 1
  • Nevena Grdović
    • 1
  • Mirunalini Ravichandran
    • 2
  • Tomasz P. Jurkowski
    • 2
  1. 1.Institute for Biological ResearchUniversity of BelgradeBelgradeSerbia
  2. 2.Institute of BiochemistryUniversity of StuttgartStuttgartGermany
  3. 3.Department of Molecular Biology, Institute for Biological Research Siniša StankovićUniversity of BelgradeBelgradeSerbia

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