Animal Models of Epigenetic Regulation in Neuropsychiatric Disorders

Abstract

Epigenetics describes the phenomenon of heritable changes in gene regulation that are governed by non-Mendelian processes, primarily through biochemical modifications to chromatin structure that occur during cell development and differentiation. Numerous lines of evidence link abnormal levels of chromatin modifications (either to DNA, histones, or both) in patients with a wide variety of diseases including cancer, psychiatry, neurodegeneration, metabolic and inflammatory disorders. Drugs that target the proteins controlling chromatin modifications can modulate the expression of clusters of genes, potentially offering higher therapeutic efficacy than classical agents with single target pharmacologies that are susceptible to biochemical pathway degeneracy. Here, we summarize recent research linking epigenetic dysregulation with diseases in neurosciences, the application of relevant animal models, and the potential for small molecule modulator development to facilitate target discovery, validation and translation into clinical treatments.

Keywords

Chromatin Epigenetics Histone modifying enzymes Inhibitors 

Abbreviations

2-OG

2-Oxo-glutarate

AAV

Adeno-associated virus

BDNF

Brain-derived neurotrophic factor

BET

Bromodomain and extra C-terminal domain protein

CaMK

Ca2+/calmodulin-dependent protein kinase

CDK5

Cyclin-dependent kinase 5

ChIP

Chromatin immunoprecipitation

CoA

Coenzyme A

CpG

Short stretches of DNA in which the frequency of C and G base pairs are higher than other regions

CREB

cAMP response element binding protein

CRH

Corticotrophin releasing hormone

CTCL

Cutaneous T-cell lymphoma

DNMT

DNA methyltransferase

FAD

Flavin adenine dinucleotide

FPC

Frontopolar cortex

FRET

Forster resonance energy transfer

GABA

Gamma-aminobutyric acid

GR

Glucocorticoid receptor

H3K9Me2

Histone H3 dimethylated at lysine-9 ε-nitrogen

HAT

Histone acetyl transferase

HDAC

Histone deacetylase

HSV

Herpes simplex virus

IKB

IκB transcription factor

IKK

IκB kinase

JMJD

Jumonji (demethylase) domain

KDM

Lysine demethylase

KO

Knockout

LG

Licking and grooming

LSL

Lox P-stop-Lox P cassette

LTP

Long-term potentiation

MAOI

Monoamine oxidase inhibitor

MBD

Methyl-CpG-binding domain protein

MBT

Maligant brain tumour domain

MeCP2

Methyl CpG binding protein 2

miRNA

MicroRNA

NAc

Nucleus accumbens

NFκB

Nuclear factor-kappaB

NGFIA

Nerve growth factor inducible protein A

PHD

Plant homeodomain

PRMT

Arginine methyltransferase

PTGS

Post-transcriptional gene silencing

SAHA

Suberoyl-aniline hydroxamic acid

SirT

Sirtuin (NAD+-dependent histone deacetylase)

SUMO

Small ubiquitin-like modifier

TSA

Trichostatin A

TSS

Transcription start site

WT

Wild-type

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Copyright information

© Springer-Verlag Berlin Heidelberg 2011

Authors and Affiliations

  • Chas Bountra
    • 1
  • Udo Oppermann
    • 1
    • 2
  • Tom D. Heightman
    • 1
  1. 1.Structural Genomics ConsortiumUniversity of OxfordOxfordUK
  2. 2.Botnar Research Centre, Oxford Biomedical Research UnitUniversity of OxfordOxfordUK

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