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Role of DNMTs in the Brain

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DNA Methyltransferases - Role and Function

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1389))

Abstract

DNA methyltransferases (DNMTs) are widely expressed in the brain, dictating the transcriptional activity of genes through various epigenetic mechanisms. Functional irregularities, alterations in the activity, and aberrant expression levels of DNMTs have been linked to various neurodevelopmental abnormalities, neuropsychiatric disorders, neurodegenerative diseases, and brain cancer. A continuously increasing number of studies address the roles DNMTs have in the brain, to reach a better understanding of their involvement in disease-related pathophysiologies, which in turn is required to dissect their applicability as potential therapeutic targets. This chapter provides an overview of DNMT function in the developing and the adult brain, putting a spotlight on their role in orchestrating diverse aspects of brain development, memory, and aging, followed by a discussion of associated neurodevelopmental and neurodegenerative disorders, and the implications in brain cancer.

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Abbreviations

5-AZA:

5-azacytidine

5-hmC:

5-hydroxymethylcytosine

5-mC:

5-methylcystosinee

Aβ:

Amyloid-beta protein

AD:

Alzheimer’s disease

aIPC:

Apical intermediate progenitor cells

APP:

Amyloid precursor protein

ARC:

Activity regulated cytoskeletal-associated protein

BAX:

Bcl-2-associated X protein

BCL2:

B-cell lymphoma 2

BCL2L2:

Bcl-2-like protein 2

BDNF:

Brain-derived neurotrophic factor

bIPC:

Basal intermediate progenitor cells

BIRC5:

Baculoviral inhibitor of apoptosis repeat-containing 5; Survivin

bRGC:

Basal radial glial cells

cAMP:

Cyclic adenosine monophosphate

CASP8:

Caspase-8

CDK5:

Cyclin-dependent kinase 5

CDKN2A:

Cyclin-dependent kinase inhibitor 2A

CGE:

Caudal ganglionic eminence

CNS:

Central nervous system

CpG:

Cytosine-phosphate-guanine

CREB:

cAMP response element-binding protein

CRISPR:

Clustered regularly interspaced short palindromic repeats

CTCF:

CCCTC-binding factor

CTIP2:

B-cell lymphoma/leukemia 11B

dCGE:

Dorsal caudal ganglionic eminence

DNA:

Deoxyribonucleic acid

DNMT:

DNA methyltransferase

E-LTP:

Early long-term potentiation

EZH2:

Enhancer of zeste homolog 2

GABA:

Gamma aminobutyric acid

GBM:

Glioblastoma

GFAP:

Glial fibrillary acidic protein

GluN2A:

N-methyl d-aspartate receptor subtype 2A

GSK3B:

Glycogen synthase kinase 3 beta

H3K27me3:

Trimethylation of lysine 27 on histone H3

H3K4me3:

Trimethylation of lysine 4 on histone H3

H3K9me3:

Trimethylation of lysine 9 on histone H3

HD:

Huntington’s disease

HIC1:

Hypermethylated in cancer 1 protein

HTT:

Huntingtin protein

ICF:

Immunodeficiency, centromere region instability, facial anomalies syndrome

IDH:

Isocitrate dehydrogenase

IPC:

Intermediate progenitor cells

iPSC:

Induced pluripotent stem cell

iSVZ:

Inner subventricular zone

JAK:

Janus kinase

L-LTP:

Late long-term potentiation

lncRNA:

Long non-coding RNA

LTD:

Long-term depression

LTP:

Long-term potentiation

MAPT:

Microtubule-associated protein TAU

MBD:

Methyl-binding domain

MeCP2:

Methyl-CpG binding protein 2

MGE:

Medial ganglionic eminence

MGMT:

O6-alkylguanine DNA alkyltransferase

mHTT:

Mutant Huntingtin protein

miRNA:

Micro RNA

mRNA:

Messenger RNA

MZ:

Marginal zone

NDD:

Neurodegenerative diseases

NF2:

Neurofibromin 2; Merlin

NFIA:

Nuclear factor 1 A-type

NMDA:

N-methyl-d-aspartic acid

NMDAR:

N-methyl-d-aspartic acid receptor

NPY:

Neuropeptide Y

oSVZ:

Outer subventricular zone

p21:

Cyclin-dependent kinase inhibitor 1

PAK6:

p21 activated kinase 6

PDGFRA:

Platelet-derived growth factor receptor A

PET:

Positron emission tomography

piRNA:

Piwi-interacting RNA

POa:

Pre-optic area

PR C2:

Polycomb repressive complex 2

PSEN:

Presenilin

PTCH1:

Protein patched homolog 1

PV:

Parvalbumin

REST:

RE1-silencing transcription factor

RG108:

N-Phthalyl-l-tryptophan

RGC:

Radial glial cell

RNA:

Ribonucleic acid

SCZ:

Schizophrenia

SFRP:

Secreted frizzled-related protein

SHH:

Sonic-Hedgehog

sncRNA:

Small non-coding RNA

SST:

Somatostatin

STAT:

Signal transducer and activator of transcription

SVZ:

Sub-ventricular zone

TBRS:

Tatton-Brown-Rahman syndrome

TET:

Ten-eleven translocation enzyme

TF:

Transcription factor

TMS1:

PYD and CARD domain containing, transcript variant 1

TMZ:

Temozolomide

VIP:

Vasointestinal peptide

VZ:

Ventricular zone

Wnt:

Wingless and Int-1

ZIF268:

Zinc finger protein 268; Early growth response protein 1

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Authors and Affiliations

  1. Functional Epigenetics in the Animal Model, Institute for Biology II, RWTH Aachen University, Aachen, Germany

    Can Bora Yildiz & Geraldine Zimmer-Bensch

  2. Research Training Group 2416 MultiSenses-MultiScales, Institute for Biology II, RWTH Aachen University, Aachen, Germany

    Can Bora Yildiz & Geraldine Zimmer-Bensch

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  1. Can Bora Yildiz
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Correspondence to Geraldine Zimmer-Bensch .

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  1. Department of Biochemistry, Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Stuttgart, Germany

    Albert Jeltsch

  2. School of Biosciences, Division of Biomedicine, Cardiff University, Cardiff, UK

    Renata Z. Jurkowska

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This research was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—368482240/GRK2416DFG; DFG ZI1224/8-1; DFG ZI1224/13-1.

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Yildiz, C.B., Zimmer-Bensch, G. (2022). Role of DNMTs in the Brain. In: Jeltsch, A., Jurkowska, R.Z. (eds) DNA Methyltransferases - Role and Function. Advances in Experimental Medicine and Biology, vol 1389. Springer, Cham. https://doi.org/10.1007/978-3-031-11454-0_15

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