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pp 1-32 | Cite as

Chemical Compounds Targeting DNA Methylation and Hydroxymethylation

  • Roman Belle
  • Akane KawamuraEmail author
  • Paola B. ArimondoEmail author
Chapter
Part of the Topics in Medicinal Chemistry book series

Abstract

DNA methylation and its oxidised forms participate in the interpretation and regulation of the human genome. Many questions arise around the enzymes responsible for these chemical modifications on DNA, and their roles in transcriptional regulation. These epigenetic marks are very dynamic and specific in their location and context (tissues, diseases, etc.). We review the major enzymes involved in DNA methylation and oxidation, with a focus on the DNA methyltransferases and TET enzymes. The principal compounds that inhibit these enzymes are presented since they will help address these questions.

Keywords

DNA hydroxymethylation DNA methylation DNMT Inhibitors TET 

Abbreviations

1-mA

1-Methyl-adenine

2OG

2-Oxoglutarate

3-mC

3-Methylcytosine

3-mT

3-Methyl-thymine

5-aza-C

5-Aza-cytosine

5-azadC

5-Aza-2′-deoxycytosine

5-caC

5-Carboxycytosine

5-fC

5-Formylcytosine

5-hmC

5-Hydroxymethylcytosine

5-mC

5-Methylcytosine

5-xC

5-Modified cytosine

6-mA

6-Methyl-adenine

AML

Acute myeloid leukaemia

AM-PD

Active modification-passive dilution

BAH1 and BAH2

Bromo-adjacent homology domains 1 and 2

BER

Base excision repair

CFP1

CpG-binding protein, CXXC finger protein 1

CMML

Chronic myelomonocytic leukaemia

CpA

Cytidine pairing adenosine

CpC

Cytidine pairing cytidine

CpG

Cytidine pairing guanosine

CpT

Cytidine pairing thymidine

CXXC

CXXC domain

DMAP domain

DNA methyltransferase-associated protein 1-interacting domain

DNMT

C5-DNA methyltransferase

DSBH

Double-stranded β-ηelix

EGCG

Epigallocatechin gallate

ELISA

Enzyme-linked immunosorbent assay

EMA

European Medicines Agency

FDA

Food and Drug Administration

FH

Fumarate hydratase

FTO

Fat mass and obesity-associated protein

HDAC

Histone deacetylase

IDAX

Inhibition of the Dvl and Axin complex

IDH

Isocitrate dehydrogenase

LCI

Low-complexity insert

LC-MS

Liquid chromatography-mass spectrometry

MALDI-TOF

Matrix-assisted laser desorption/ionisation time-of-flight

MBP

Methyl-binding protein

MDS

Myelodysplastic syndrome

MLL

Mixed lineage leukaemia

mTet1

Murine TET

NgTet1

Naegleria gruberi TET

NLS

Nuclear localisation signal

NOG

N-Oxalylglycine

PBD

PCNA-binding domain

PHD

Plant homeodomain

PRMT

Protein arginine methyltransferase

PWWP

Proline-tryptophan-tryptophan-proline domain

R/S-2HG

R/S-2-hydroxyglutarate

RFTD

Replication foci targeting sequence (RFTS) domain

ROS1

Repressor of silencing 1

SAH/AdoHys

S-Adenosyl-l-homocysteine

SAM/AdoMet

S-Adenosyl-l-methionine

SDH

Succinate dehydrogenase

SPR

Surface plasmon resonance

TCA

Tricarboxylic acid

TDG

Thymidine-DNA glycosylase

TET

Ten-eleven translocation

TLC

Thin-layer chromatography

TRDMT1

tRNA aspartic acid methyltransferase

Notes

Acknowledgement

RB is supported by the Engineering and Physical Science Research Council and University of Oxford. AK gratefully acknowledges the Royal Society for the Dorothy Hodgkin Fellowship and the European Research Council Starting Grant (EPITOOLS-679479) and the Cancer Research UK Oxford Centre Development Fund (C5255/A18085). We apologise for the incomplete citations of research due to space constraints.

The authors acknowledge the EU COST Action CM1406. PBA is supported by PlanCancer2014-2019 (EPIG-2014-01).

Compliance with Ethical Standards

Funding: RB is supported by the Engineering and Physical Science Research Council and University of Oxford. AK gratefully acknowledges the Royal Society for the Dorothy Hodgkin Fellowship and the European Research Council Starting Grant (EPITOOLS-679479) and the Cancer Research UK Oxford Centre. We apologise for the incomplete citations of research due to space constraints.

The authors acknowledge the EU COST Action CM1406. PBA is supported by PlanCancer 2014–2019 (EPIG-2014-01). PBA was recipient of the French Oversea Fellowship of the French Government and Churchill College Cambridge UK.

Conflict of Interest:

Roman Belle declares that he has no conflict of interest. Akane Kawamura declares that she has no conflict of interest and Paola B. Arimondo declares that she has no conflict of interest.

Ethical Approval:

This chapter does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer Nature Switzerland AG  2019

Authors and Affiliations

  1. 1.Department of ChemistryUniversity of Oxford, Chemistry Research LaboratoryOxfordUK
  2. 2.Radcliffe Department of MedicineUniversity of Oxford, Wellcome Centre for Human GeneticsOxfordUK
  3. 3.Epigenetic Chemical BiologyInstitut Pasteur, CNRS UMR3523ParisFrance

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