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The Human Epigenome

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Epigenetic Epidemiology

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Abstract

The output of the genome is controlled by the interaction of transcription factors with the epigenome. Epigenetic processes such as DNA methylation, histone modification, histone variants, noncoding RNAs, and nucleosomal remodeling machines interact with each other to ensure stable states of gene expression. These processes can become dysregulated during aging, exposure to environmental stressors, and the development of cancer and other diseases. DNA methylation patterns can be relatively easily read by high throughput techniques and provide information reflecting the influence of the environment and aging on the functionality of the epigenome. Analysis of DNA methylation patterns, therefore, provides an exciting new route to understanding how the environment interacts with the epigenome to cause disease. Despite the promise of DNA methylation patterns for epidemiologic studies, caution in interpreting data from surrogate tissues is necessary and cellular heterogeneity can also complicate interpretation of the data. In addition, DNA methylation within the body of genes can influence the response of the genome to the environment. Hypomethylation of repetitive elements can lead to genomic instability and ectopic gene expression. Methylation of coding regions can directly increase the rate of spontaneous hydrolytic mutations and increase the mutational frequency induced by carcinogens and radiation. Epigenetic processes can therefore contribute in multiple ways to the development of human diseases particularly cancer.

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Abbreviations

5mC:

5-methylcytosine

5hmC:

5-hydroxymethylcytosine

5fC:

5-formylcytosine

5caC:

5-carboxylcytosine

CHD:

Chromodomain Helicase DNA binding protein

ChIP:

Chromatin immunoprecipitation

DNMT1:

DNA methyltransferase 1

DNMT3A:

DNA methyltransferase 3A

DNMT3B:

DNA methyltransferase 3B

eRNA:

enhancer RNA

ecRNA:

extra-coding RNA

ISWI:

imitation SWItch

KDM:

lysine demethylase

lncRNA:

long noncoding RNA

ncRNA:

noncoding RNA

OxBS:

oxidative bisulfite sequencing

PRC2:

Polycomb Repressive Complex 2

SAM:

S-adenosine methionine

SWI/SNF:

SWItch/Sucrose Non-Fermentable

TAB-seq:

Tet-assisted bisulfite sequencing

TDG:

thymine DNA glycosylases

TETs:

Ten-eleven translocation enzymes

UDG:

uracil DNA glycosylases

UHRF1:

Ubiquitin-like, containing PHD and RING finger domains, 1

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Authors and Affiliations

  1. Department of Epigenetics, Van Andel Institute, Grand Rapids, MI, USA

    Rochelle L. Tiedemann, Gangning Liang & Peter A. Jones

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  1. Rochelle L. Tiedemann
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  2. Gangning Liang
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  3. Peter A. Jones
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Correspondence to Peter A. Jones .

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  1. Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, USA

    Karin B. Michels

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Tiedemann, R.L., Liang, G., Jones, P.A. (2022). The Human Epigenome. In: Michels, K.B. (eds) Epigenetic Epidemiology. Springer, Cham. https://doi.org/10.1007/978-3-030-94475-9_1

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