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Preventing and Diagnosing Diabetic Complications: Epigenetics, miRNA, DNA Methylation, and Histone Modifications

Applications of miRNA, DNA Methylation, and Histone Modifications on Diagnosis and Therapeutics of Diabetic Embryopathy
  • Daoyin Dong
  • E. Albert Reece
  • Peixin YangEmail author
Reference work entry

Abstract

In previous chapter of this book, we have elucidated that three epigenetic modalities – microRNA (miRNA), DNA methylation, and histone modifications – are possible pathological pathways causing diabetic embryopathy. This chapter discusses the potential of utilizing epigenetic biomarkers for early diagnosis of embryonic malformation in pregnancy, and the therapeutics for diabetic embryopathy based on modifying epigenetic changes. We show evidence that circulating miRNAs, intermediates of the DNA methylation cycle, and epigenetic profiles of circulating nucleosomes, such as DNA methylation and histone modifications, have become promising biomarker candidates for diagnosis and prognosis of diabetic embryopathy. We also describe studies which have targeted the activity of hyperglycemia-induced miRNAs, using mimics or inhibitors; DNA methylation, using nutritional supplements; and histone modifying enzymes, using chemical inhibitors, to prevent diabetic embryopathy. Although we have the promising progress, the development of effective biomarkers and therapeutics for diabetic embryopathy still face many challenges.

Keywords

Maternal diabetes Embryopathy miRNA DNA methylation Histone modifications Biomarker Therapeutics 

List of Abbreviations

5MC

5-methylcytosine

CHD

Congenital heart defect

DM

Diabetes mellitus

Dnmt

DNA methyltransferase

EGCG

Polyphenol epigallocatechin gallate

FXN

Frataxin

Grhl3

Grainyhead like transcription factor 3

H3K27me3

Histone 3 lysine 27 trimethylation

H3K4me2

Histone 3 lysine 4 bimethylation

H3K9me3

Histone 3 lysine 9 trimethylation

H4K20me3

Histone 4 lysine 20 trimethylation

Hcy

Homocysteine

KCNH2

Potassium voltage-gated channel subfamily H member 2;

KCNQ1

Potassium voltage-gated channel subfamily Q member 1

LINE-1

Long interspersed nuclear element-1

MYH6

Myosin heavy chain 6

NTD

Neural tube defect

Pax3

Paired box 3

SAH

S-Adenosylhomocysteine

SAM

S-adenosylmethionine

TSA

Trichostatin A

Tulp3

Tubby like protein 3

VPA

Valproic acid

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© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019

Authors and Affiliations

  1. 1.Department of Obstetrics, Gynecology and Reproductive SciencesUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.Department of Biochemistry and Molecular BiologyUniversity of Maryland School of MedicineBaltimoreUSA

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