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Embryopathy as a Model for the Epigenetics Regulation of Complications in Diabetes

The Roles of miRNA, DNA Methylation, and Histone Modification in Induction of Diabetic Embryopathy
  • Daoyin Dong
  • E. Albert Reece
  • Peixin Yang
Reference work entry

Abstract

Pregestational diabetes mellitus is a serious public health problem and a high-risk factor for diabetes-associated birth defects, such as neural tube defects (NTDs), congenital heart defects (CHDs), and susceptibility to postnatal diseases in the offspring. Over the past several decades, studies on the etiology of diabetic embryopathy have implicated epigenetic factors as an underlying cause for maternal diabetes-induced congenital developmental defects. Three epigenetic modalities – microRNA (miRNA), DNA methylation, and histone modification – are possible pathological pathways causing diabetic embryopathy. This chapter discusses the implication of epigenetic alterations in causing diabetic embryopathy. We highlight current studies which have demonstrated that maternal diabetes-altered miRNAs, DNA methylation, and histone modifications disturb embryonic developmental processes via inhibition of genes involved in stem cell proliferation and differentiation and activation of proapoptotic genes, thereby leading to embryonic malformation. Despite these promising studies, the detailed roadmap of how maternal diabetes causes epigenetic alterations which contribute to diabetic embryopathy is still elusive.

Keywords

Maternal diabetes Embryopathy Neural tube defects Congenital heart defects miRNA DNA methylation Histone modifications 

List of Abbreviations

ASK1

Apoptosis signal-regulating kinase 1

CHD

Congenital heart defect

Cited2

CBP/p300-interacting transactivator with ED-rich tail 2

CLDN1

Claudin 1

CTGF

Connective tissue growth factor

Dcx

Doublecortin

DM

Diabetes mellitus

Dnmt

DNA methyltransferase

ER

Endoplasmic reticulum

Est1

E26 avian leukemia oncogene 1, 5′ domain

GATA4

GATA binding protein 4

Grhl3

Grainyhead like transcription factor 3

GSK3β

Glycogen synthase kinase-3 beta

H3K14ac

Histone 3 lysine 14 acetylation

H3K27ac

Histone 3 lysine 27 acetylation

H3K56ac

Histone 3 lysine 56 acetylation

H3K9ac

Histone 3 lysine 9 acetylation

H3K9me3

Histone 3 lysine 9 trimethylation

H4K16ac

Histone 4 lysine 16 acetylation

IGF-1

Insulin-like growth factor 1

IRE1α

Inositol-requiring enzyme 1 alpha

Mef2c

Myocyte enhancer factor 2C

microRNA

miRNA

MSX1

msh homeobox 1

MTHFR

Methylenetetrahydrofolate reductase

NTD

Neural tube defect

Pafah1b1

Platelet activating factor acetyl hydrolase, isofrom 1b, subunit 1

Pax3

Paired box 3

SIRT

Sirtuin

STAT3

Signal transducer and activator of transcription 3

TRAF3

TNF receptor-associated factor 3

TSP1

Thrombospondin 1

Tulp3

Tubby like protein 3

Txnip

Thioredoxin-interacting protein

Zeb2

Zinc finger E-box binding homeobox 2

5MC

5-methylcytosine

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Copyright information

© 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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