Epigenetics and environmental health

doi:10.1007/s11684-023-1038-2

Front. Med.

2024, Vol. 18

Issue (4) : 571-596 https://doi.org/10.1007/s11684-023-1038-2

Epigenetics and environmental health

Min Zhang¹, Ting Hu¹, Tianyu Ma^1,², Wei Huang²(

), Yan Wang^1,²(

)

¹. Key Laboratory of Cancer and Microbiome, State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
². Beijing Key Laboratory of Cancer Invasion and Metastasis Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China

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Abstract

Epigenetic modifications including DNA methylation, histone modifications, chromatin remodeling, and RNA modifications complicate gene regulation and heredity and profoundly impact various physiological and pathological processes. In recent years, accumulating evidence indicates that epigenetics is vulnerable to environmental changes and regulates the growth, development, and diseases of individuals by affecting chromatin activity and regulating gene expression. Environmental exposure or induced epigenetic changes can regulate the state of development and lead to developmental disorders, aging, cardiovascular disease, Alzheimer’s disease, cancers, and so on. However, epigenetic modifications are reversible. The use of specific epigenetic inhibitors targeting epigenetic changes in response to environmental exposure is useful in disease therapy. Here, we provide an overview of the role of epigenetics in various diseases. Furthermore, we summarize the mechanism of epigenetic alterations induced by different environmental exposures, the influence of different environmental exposures, and the crosstalk between environmental variation epigenetics, and genes that are implicated in the body’s health. However, the interaction of multiple factors and epigenetics in regulating the initiation and progression of various diseases complicates clinical treatments. We discuss some commonly used epigenetic drugs targeting epigenetic modifications and methods to prevent or relieve various diseases regulated by environmental exposure and epigenetics through diet.

Keywords epigenetics environmental exposure health prevention and therapy

Corresponding Author(s): Wei Huang,Yan Wang

Just Accepted Date: 07 February 2024 Online First Date: 24 May 2024 Issue Date: 30 August 2024

Cite this article:

Min Zhang,Ting Hu,Tianyu Ma, et al. Epigenetics and environmental health[J]. Front. Med., 2024, 18(4): 571-596.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-023-1038-2
https://academic.hep.com.cn/fmd/EN/Y2024/V18/I4/571

Fig.1 Epigenetic modifications. Epigenetic modifications include chromatin remodeling, DNA methylation, histone modifications (histone methylation (Me), acetylation (Ac), phosphorylation (P), ubiquitylation (Ub), ADP ribosylation (Ar), lactylation (La), sumoylation (Su), citrullination (Cit)), RNA modifications (m⁶A modifications and noncoding (nc) RNA).

Fig.2 Epigenetic modifications influence health by regulating gene expression. Epigenetic modifications such as chromatin remodeling, DNA methylation, histone modifications, and RNA modifications can regulate gene expression through permissive or repressive modifications.

Fig.3 Environmental exposure influences health through epigenetic regulation of gene expression. Environmental exposure to air pollution, light pollution, smoking, alcohol, and sugar influences epigenetic modifications that further regulate gene expression by permissive or repressive modifications to affect the overall health of the human body.

Fig.4 DNA methylation induced by environmental exposure. In the process of DNA demethylation, passive DNA demethylation, wherein methylated cytosines are diluted in the genome owing to the loss of methylation enzymes. In the process of DNA demethylation, 5mC is initially oxidized to 5-hydroxymethyl cytosine (5hmC), then oxidized to 5-formylcytosine (5fC), further oxidized to 5-carboxycytosine (5caC). Thymine DNA glycosylase (TDG) removes 5fC and 5caC from the DNA to produce unmodified C.

Fig.5 Histone modification state changes induced by environmental factors. Changes in histone modification status is one of the key links between the interaction of the body and environmental factors. Various environmental factors can influence the histone modification status of cells. This mainly affects the methylation and acetylation levels of histones H3 and H4 that regulate the expression of downstream proteins and signaling pathways, and ultimately realize the cell response to environmental factors.

Fig.6 Chromatin remodeling induced by environmental exposure. Histone deacetylases (HDACs), histone acetyltransferases (HATs), histone demethylases (HDMs), histone methyltransferases (HMTs), and DNA methyltransferases (DNMTs) regulate gene expression by modifying histones or DNA, and ATP-dependent chromatin remodelers participate in regulating the condensation and relaxation of chromatin after environmental exposure.

Fig.7 RNA modification induced by environmental exposure. The adenosine (A) bases residing in mRNA (ZBTB4, TP53, IFNB1, and ANLKLE) can be methylated by the core component of the METTL3–METTL14–WTAP complex or METTL16 alone and other regulatory cofactors to form N⁶-methyladenosine (m⁶A) after environmental exposure. S-Adenosyl methionine (SAM) is a methyl donor in enzymatic reactions. m⁶A of mRNA can be removed by m⁶A eraser proteins (FTO or ALKBH5) or recognized by m⁶A binding proteins to further affect mRNA fate in response to environmental exposure. Demethylation of mRNA requires α-ketoglutaric acid as a cofactor. JHDM, Jumonji domain-containing histone demethylase; TET1/2, ten-11 translocation methylcytosine dioxygenase 1/2; α-KG, α-ketoglutarate. Noncoding RNAs such as microRNAs and lncRNAs are methylated and affect target genes under certain environmental conditions.

Fig.8 Pb exposure influences disease initiation and progression. Pb exposure influences various gene expressions through different signal pathways or genes and epigenetics crosstalk, further regulating the initiation and progression of diseases.

Tab.1 Common epigenetic inhibitors targeting epigenetic modification alterations induced by environmental exposure

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