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Epigenome Changes During Development

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Epigenetic Epidemiology

Abstract

Epigenetic modifications accomplish the functional compartmentalisation of our genome. They ensure a high level of compaction of our DNA in a manner that nonetheless allows genes vital to given cell types to be expressed appropriately whilst sequestering away silent genes. The stability of epigenetic modifications provides long term memory in phenomena such as X-chromosome inactivation in females and genomic imprinting, but epigenetic states must also be dynamic as they are intimately involved in establishing the gene expression programmes that define cell lineage and are required to register changes in the environment. In this chapter, I shall describe the major epigenomic events that occur during mammalian development, from the specification of germ cells, to how the epigenome differences of the gametes are resolved at fertilisation, and how epigenomic events contribute to and reinforce lineage determination events. The advent of genome-wide profiling technologies is providing us with an unprecedented opportunity to investigate the scale of epigenomic changes during development and differentiation and how epigenomes are altered in disease.

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Abbreviations

Avy :

agouti viable yellow allele

Bi-Seq:

bisulphite whole genome sequencing

BMP4:

bone morphogenic protein 4

c-Kit:

v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

CARM1:

co-activator associated arginine methyltransferase 1

Cdx2:

caudal type homeobox 2

Cfp1:

CXXC finger protein 1

ChIP-Seq:

chromatin immunopreciptation combined with next generation sequencing

Dnmt1:

DNA methyltransferase 1

Dnmt3a:

DNA methyltransferase 3a

Dnmt3b:

DNA methyltransferase 3b

Dnmt3L:

DNA methyltransferase 3-like

DMR:

differentially methylated region (of an imprinted gene)

EHMT2:

euchromatic histone methyltransferase 2

ELF5:

ETS-related family transcription factor 5

EOMES:

eomesodermin

ES:

embryonic stem

Ezh2:

Enhancer of zeste homologue 2

GCs:

germ cells

H1T2:

histone 1 variant T2

H1LS1:

histone 1 variant LS1

H2:

histone H2

H2A.Z:

histone 2a variant Z

H2AR3me2:

di-methylated H2A arginine 3

H3:

histone H3

H3.3:

histone 3 variant 3

H3K4:

H3 lysine 4

H3K4me1/2/3:

mono-/di- or tri-methylated H3 lysine 4

H3K9ac:

acetylated H3 lysine 9

H3K9me1/2/3:

mono-/di- or tri-methylated H3 lysine 9

H3K18ac:

acetylated H3 lysine 18

H3K27me3:

tri-methylated H3 lysine 37

H3K36me3:

tri-methylated H3 lysine 36

H4K20me3:

tri-methylated H4 lysine 20

H4:

histone H4

H4R3me2:

di-methylated H4 arginine 3

IAP:

intracisternal A particle

ICM:

inner cell mass

ICR:

imprinting control region

Igf2 :

insulin-like growth factor 2 gene

iPSCs:

induced pluripotential stem cells

KAP1:

KRAB (Krüppel-associated box)-associated protein 1

KDM1B:

lysine (K)-specific demethyase 1B

KDM2A:

lysine (K)-specific demethyase 2A

Klf2:

Krüppel-like factor 2

LTR:

long terminal repeat

MeDIP-chip:

methylcytosine immunoprecipitation combined with microarray hybridisation

NIH:

National Institutes of Health

NLRP2:

NLR family Pyrin domain containing protein 2

NLRP7:

NLR family Pyrin domain containing protein 7

PcG:

Polycomb group

PGCs:

primordial germ cells

Pparα :

peroxisome proliferator-activated receptor alpha

PRC2:

Polycomb group (PcG) repressor complex 2

Prdm1(Blimp1):

PR domain containing 1

PRDM9:

PR domain containing protein 9

Prdm14:

PR domain containing protein 14

Prmt5:

protein arginine methyltransferase 5

RdDM:

RNA-directed DNA methylation

Sox2:

SRY (sex determining region Y)-box 2

Suv39h1/2:

suppressor of variegation 3-9 homolog 1 & 2

TE:

trophoectoderm

Tet1:

ten-eleven translocation 5mc-hydrolase 1

Tet3:

ten-eleven translocation 5mc-hydrolase 3

TNP1 & 2:

transition protein 1 & 2

Uhrf1:

ubiquitin-like containing PHD and RING finger domains 1

ZFP57:

zinc-finger protein 57

5mC:

5-methylcytosine

5hmC:

5-hydroxymethylcytosine

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Authors and Affiliations

  1. Epigenetics Programme, The Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK

    Gavin Kelsey

  2. Centre for Trophoblast Research, University of Cambridge, Cambridge, CB2 3EG, UK

    Gavin Kelsey

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  1. Gavin Kelsey
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Correspondence to Gavin Kelsey .

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  1. , Obstetrics and Gynecology Epidemiology D, Brigham and Women’s Hospital, Longwood Avenue 221, Boston, 02115, Massachusetts, USA

    Karin B. Michels

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Kelsey, G. (2012). Epigenome Changes During Development. In: Michels, K. (eds) Epigenetic Epidemiology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2495-2_6

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