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Genetic Studies on Mammalian DNA Methyltransferases

  • Jiameng Dan
  • Taiping ChenEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 945)

Abstract

Cytosine methylation at the C5-position, generating 5-methylcytosine (5mC), is a DNA modification found in many eukaryotic organisms, including fungi, plants, invertebrates, and vertebrates, albeit its levels vary greatly in different organisms. In mammals, cytosine methylation occurs predominantly in the context of CpG dinucleotides, with the majority (60–80 %) of CpG sites in their genomes being methylated. DNA methylation plays crucial roles in the regulation of chromatin structure and gene expression and is essential for mammalian development. Aberrant changes in DNA methylation levels and patterns are associated with various human diseases, including cancer and developmental disorders. DNA methylation is mediated by three active DNA methyltransferases (Dnmts), namely, Dnmt1, Dnmt3a, and Dnmt3b, in mammals. Over the last two decades, genetic manipulations of these enzymes, as well as their regulators, in mice have greatly contributed to our understanding of the biological functions of DNA methylation in mammals. In this chapter, we discuss genetic studies on mammalian Dnmts, focusing on their roles in embryogenesis, cellular differentiation, genomic imprinting, and X-chromosome inactivation.

Keywords

DNA methylation Dnmt1 Dnmt3a Dnmt3b Dnmt3L Genomic imprinting X-chromosome inactivation 

Abbreviations

5caC

5-Carboxylcytosine

5fC

5-Formylcytosine

5hmC

5-Hydroxymethylcytosine

5mC

5-Methylcytosine

ADCA-DN

Autosomal dominant cerebellar ataxia deafness and narcolepsy

ADD

ATRX-Dnmt3-Dnmt3L

AML

Acute myeloid leukemia

BAH

Bromo-adjacent homology

DKO

Double knockout

DMR

Differentially methylated region

DNMT

DNA methyltransferase

ES

Embryonic stem

EST

Expressed sequence tag

HP1

Heterochromatin protein 1

HSAN IE

Hereditary sensory and autonomic neuropathy with dementia and hearing loss type IE

ICF

Immunodeficiency centromeric instability and facial anomalies

ICM

Inner cell mass

ICR

Imprinting control region

KAP1

KRAB-associated protein 1

KRAB

Krüppel-associated box

lncRNA

Long non-coding RNA

MBD3

Methyl CpG-binding domain protein-3

MEF

Mouse embryonic fibroblast

MTA2

Metastasis tumor antigen 2

NLS

Nuclear localization signal

NuRD

Nuclear remodeling and histone deacetylation

PBD

PCNA-binding domain

PCNA

Proliferating cell nuclear antigen

PGC

Primordial germ cell

PHD

Plant homeodomain

PRC2

Polycomb repressive complex 2

PWWP

Proline-tryptophan-tryptophan-proline

RFTS

Replication foci-targeting sequence

RING

Really Interesting New Gene

SRA

SET- and RING-associated

TDG

Thymine DNA glycosylase

TTD

Tandem tudor domain

UBL

Ubiquitin-like

Uhrf1

Ubiquitin-like with PHD and RING finger domains 1

Xa

Active X chromosome

XCI

X-chromosome inactivation

Xi

Inactive X chromosome

Xic

X-inactivation center

Xist

X-inactive-specific transcript

Xm

Maternal X chromosome

Xp

Paternal X chromosome

Notes

Acknowledgments

Work in the Chen laboratory is supported by a Rising Star Award from Cancer Prevention and Research Institute of Texas (CPRIT, R1108) and a grant from the National Institutes of Health (NIH, 1R01DK106418-01).

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Epigenetics and Molecular CarcinogenesisThe University of Texas MD Anderson Cancer CenterSmithvilleUSA
  2. 2.Center for Cancer EpigeneticsThe University of Texas MD Anderson Cancer CenterSmithvilleUSA
  3. 3.Graduate School of Biomedical Sciences at HoustonHoustonUSA

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