The Emerging Role of Ten-Eleven Translocation 1 in Epigenetic Responses to Environmental Exposures

Zhu, Tao; Brown, Anthony P.; Ji, Hong

doi:10.1177/2516865720910155

Cited by 18 publications

(18 citation statements)

References 87 publications

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“…In recent years, researches on hydromethylation mainly focus on tumors and psychiatric diseases [104,105]. Studies have shown that during organ maturation and drug-induced response, 5hmC analysis can be used as an indicator of cell status and contribute to the identification of toxic carcinogen exposure [106,107]. Dynamic enrichment patterns of methylation and hydromethylation markers may enable us to identify target genes for epigenetic modifications associated with prostate cancer [108].…”

Section: Discussionmentioning

confidence: 99%

Hydroxymethylation and tumors: can 5-hydroxymethylation be used as a marker for tumor diagnosis and treatment?

Gao

2020

Hum Genomics

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5-Methylcytosine (5mC) is considered as a common epigenetic modification that plays an important role in the regulation of gene expression. At the same time, 5-hydroxymethylcytosine (5hmC) has been found as an emerging modification of cytosine bases of recent years. Unlike 5mC, global 5hmC levels vary from tissues that have differential distribution both in mammalian tissues and in the genome. DNA hydroxymethylation is the process that 5mC oxidates into 5hmC with the catalysis of TET (ten-eleven translocation) enzymes. It is an essential option of DNA demethylation, which modulates gene expression by adjusting the DNA methylation level. Various factors can regulate the demethylation of DNA, such as environmental toxins and mental stress. In this review, we summarize the progress in the formation of 5hmC, and obtaining 5hmC in a cell-free DNA sample presents multiple advantages and challenges for the subject. Furthermore, the clinical potential for 5hmC modification in dealing with cancer early diagnosis, prognostic evaluation, and prediction of therapeutic effect is also mentioned.

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Section: Discussionmentioning

confidence: 99%

Hydroxymethylation and tumors: can 5-hydroxymethylation be used as a marker for tumor diagnosis and treatment?

Gao

2020

Hum Genomics

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“…These studies showed that CpG methylation of the GAL5.1 enhancer has a significant repressive effect on its activity in SHSY-5Y cells and confirmed previous studies demonstrating the repressive effects of 5mC on regulatory activity. However, our studies could not explore the effects of 5hmC on enhancer activity, which has been associated with increased enhancer activity [38][39][40][41]. Thanks to the recent availability of recombinant TET-proteins, that are able to convert 5mC to 5hmC, it may be possible to compare the effects of 5mC and 5hmC on GAL5.1 action in the near future [44].…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, an analysis of the effects of 5mC on the ability of 542 transcription factors (TFs) to bind DNA; an essential component of enhancer activation; found that only 23% of TFs experienced reduced binding as a result whereas the binding of 34% of TFs was actually increased by 5mC and the remaining TFs were unaffected [ 37 ]. The role of DNA methylation in influencing enhancer activity is further complicated by the influence of intermediate oxidation products of 5mC; that include 5-hydroxymethyl-cytosine (5hmC), the product of the ten-eleven translocation (TET) dioxygenase enzymes [ 38 ]. 5hmC sites are attractive to transcription factors that activate transcription [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

The anxiety and ethanol intake controlling GAL5.1 enhancer is epigenetically modulated by, and controls preference for, high-fat diet

McEwan

Erickson

Davidson

et al. 2020

Cell. Mol. Life Sci.

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Excess maternal fat intake and obesity increase offspring susceptibility to conditions such as chronic anxiety and substance abuse. We hypothesised that environmentally modulated DNA methylation changes (5mC/5hmC) in regulatory regions of the genome that modulate mood and consumptive behaviours could contribute to susceptibility to these conditions. We explored the effects of environmental factors on 5mC/5hmC levels within the GAL5.1 enhancer that controls anxiety-related behaviours and alcohol intake. We first observed that 5mC/5hmC levels within the GAL5.1 enhancer differed significantly in different parts of the brain. Moreover, we noted that early life stress had no significant effect of 5mC/5hmC levels within GAL5.1. In contrast, we identified that allowing access of pregnant mothers to high-fat diet (> 60% calories from fat) had a significant effect on 5mC/5hmC levels within GAL5.1 in hypothalamus and amygdala of resulting male offspring. Cell transfection-based studies using GAL5.1 reporter plasmids showed that 5mC has a significant repressive effect on GAL5.1 activity and its response to known stimuli, such as EGR1 transcription factor expression and PKC agonism. Intriguingly, CRISPR-driven disruption of GAL5.1 from the mouse genome, although having negligible effects on metabolism or general appetite, significantly decreased intake of high-fat diet suggesting that GAL5.1, in addition to being epigenetically modulated by high-fat diet, also actively contributes to the consumption of high-fat diet suggesting its involvement in an environmentally influenced regulatory loop. Furthermore, considering that GAL5.1 also controls alcohol preference and anxiety these studies may provide a first glimpse into an epigenetically controlled mechanism that links maternal high-fat diet with transgenerational susceptibility to alcohol abuse and anxiety.

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“…A considerable number of the enzymes participating in regulation of chromatin architecture and gene expression are apparently responsive to environmental cues. Examples are the DNA demethylating ten-eleven translocation methylcytosine dioxygenase (TET), which is up-or downregulated by several environmental factors including food ingredients, ethanol, air pollution and radiation (Zhu et al, 2020), proteins of the Polycomb group that are sensitive to the environmental temperature (Voigt & Kost, 2021), and transcription factors of the TCP family in plants that mediate environmental signals into growth responses (Danisman, 2016). In order to change gene expression, environment-sensitive proteins that are able to modify the epigenetic signatures of the chromatin and DNA must crosstalk with readers of the epigenetic marks and molecules that recruit them to specific sites of the DNA and chromatin (Figure 1).…”

Section: Generation Of Multiple Phenotypes From the Same Genotype By ...mentioning

confidence: 99%

Epigenetic ecotypes in animals: persistent environmental adaptation in the absence of genetic variation

Vogt

2022

Preprint

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According to prevailing theory, sexually reproducing animals adapt to different environments by the production of phenotypic variation from the standing genetic variation and selection of the most suited phenotypes. Contrary to all expectations, asexually reproducing animals can also inhabit broad ranges of geographical latitudes, altitudes and habitats, despite virtual genetic identity. Recent whole genome analyses of differently adapted clonal populations and genetically impoverished invaders revealed that they can use epigenetic variation instead of genetic variation to stably adapt to different environments. The required phenotypes are produced from the same DNA sequence via changes in gene expression, which is trigged by strong environmental cues and mediated by environment-sensitive epigenetic mechanisms like DNA methylation. Habitat-specific epigenetic fingerprints were maintained over subsequent years, pointing at the existence of epigenetic ecotypes. Obviously, all animals can produce different phenotypes from the same DNA sequence, but in asexually reproducing populations, genetically impoverished invaders, sessile taxa and species with long generation times it is apparently of prime importance. In contrast to beneficial genetic mutations and meiotic gene combinations that require many generations to be established in a population, environmentally-induced epigenetic changes and subsequent alterations in gene and phenotype expression affect population members synchronously in the first exposed generation, providing an ideal means for fast, directional adaptation to changing conditions. The production of different phenotypes from the same genome in response to different environmental cues via epigenetic mechanisms is also suitable to explain the “general-purpose genotype” and the “genetic paradox of invasion”.

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The Emerging Role of Ten-Eleven Translocation 1 in Epigenetic Responses to Environmental Exposures

Cited by 18 publications

References 87 publications

Hydroxymethylation and tumors: can 5-hydroxymethylation be used as a marker for tumor diagnosis and treatment?

Hydroxymethylation and tumors: can 5-hydroxymethylation be used as a marker for tumor diagnosis and treatment?

The anxiety and ethanol intake controlling GAL5.1 enhancer is epigenetically modulated by, and controls preference for, high-fat diet

Epigenetic ecotypes in animals: persistent environmental adaptation in the absence of genetic variation

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