• Toxicological Research
• /
• 제31권1호
• /
• pp.1-9
• /
• 2015

Environmental toxicants such as toxic metals can alter epigenetic regulatory features such as DNA methylation, histone modification, and non-coding RNA expression. Heavy metals influence gene expression by epigenetic mechanisms and by directly binding to various metal response elements in the target gene promoters. Given the role of epigenetic alterations in regulating genes, there is potential for the integration of toxic metal-induced epigenetic alterations as informative factors in the risk assessment process. Here, we focus on recent advances in understanding epigenetic changes, gene expression, and biological effects induced by toxic metals.

• 식품과학과 산업
• /
• 제50권1호
• /
• pp.11-15
• /
• 2017

Epigenomics is a study that analyzes and quantifies various epigenetic alterations that affect gene expressions in cells from the viewpoint of collective characteristics on biological molecular pools. DNA methylation and histone modification in cells can induce the epigenetic alterations. Especially, epigenetic alterations influenced by external factors as ingested foods and other environmental factors have been examined in the whole genome regions, which provide accumulated data of altered regions or patterns of global genome, Statistical analyses of these regions or patterns enables us to correlate epigenomic changes with human diseases in the whole genome region. Finding meaningful regulators is a major concern of epigenomic research in recent years, and these results will give the food industry an important clue to future food

• Journal of Preventive Medicine and Public Health
• /
• 제51권4호
• /
• pp.169-172
• /
• 2018

In recent years, a number of studies have been reported on the various types of cancer arising from epigenetic alterations, including reports that these epigenetic alterations occur as a result of radiation exposure or infection. Thyroid cancer and breast cancer, in particular, have high cancer burden, and it has been confirmed that radiation exposure or onco-viral infection are linked to increased risk of development of these two types of cancer, respectively. Thus, the environment-epigenetic alteration-cancer occurrence (EEC) hypothesis has been suggested. This paper reviews the trends in research supporting this hypothesis for radiation exposure and onco-viral infection. If more evidences accumulate for the EEC hypothesis from future research, those findings may greatly aid in the prevention, early diagnosis, treatment, and prognosis of the thyroid cancer and breast cancer.

• Genomics & Informatics
• /
• 제11권4호
• /
• pp.164-173
• /
• 2013

Genomic instability, which occurs through both genetic mechanisms (underlying inheritable phenotypic variations caused by DNA sequence-dependent alterations, such as mutation, deletion, insertion, inversion, translocation, and chromosomal aneuploidy) and epigenomic aberrations (underlying inheritable phenotypic variations caused by DNA sequence-independent alterations caused by a change of chromatin structure, such as DNA methylation and histone modifications), is known to promote tumorigenesis and tumor progression. Mechanisms involve both genomic instability and epigenomic aberrations that lose or gain the function of genes that impinge on tumor suppression/prevention or oncogenesis. Growing evidence points to an epigenome-wide disruption that involves large-scale DNA hypomethylation but specific hyper-methylation of tumor suppressor genes, large blocks of aberrant histone modifications, and abnormal miRNA expression profile. Emerging molecular details regarding the modulation of these epigenetic events in cancer are used to illustrate the alterations of epigenetic molecules, and their consequent malfunctions could contribute to cancer biology. More recently, intriguing evidence supporting that genetic and epigenetic mechanisms are not separate events in cancer has been emerging; they intertwine and take advantage of each other during tumorigenesis. In addition, we discuss the collusion between epigenetics and genetics mediated by heterochromatin protein 1, a major component of heterochromatin, in order to maintain genome integrity.

• 생명과학회지
• /
• 제33권9호
• /
• pp.736-745
• /
• 2023

노화란 세포 및 생리 기능이 점진적으로 손상되는 복잡한 과정이다. 알츠하이머, 동맥경화 및 갱년기와 같은 노화와 관련된 질병은 노화가 진행이 되면서 발생된다. 노화와 관련된 질환은 다양한 원인에 의해 발생된다. 그 중 유전적인 변화 없이 유전자 발현을 조절하는 후성유전의 변화는 노화, 그리고 노화와 관련된 질환의 발생에 중요한 조절자로 알려져있다. 이 리뷰에서는 후성유전의 변화가 노화 및 노화와 관련된 질병의 발전과 진행에 어떠한 역할을 하는지에 대해 서술하였다. 노화 중에 일어나는 유전적 변화의 분자적 기전과 이러한 변화가 노화와 관련된 질병에 미치는 영향, 특히 노화와 관련된 질환과 관련된 유전자 발현 양식을 조절하는 RNA 메틸화, DNA 메틸화 및 miRNA에 대해 중점적으로 초점을 맞추었다.

• Toxicological Research
• /
• 제33권1호
• /
• pp.1-5
• /
• 2017

Nuclear factor E2-related factor 2 (Nrf2), a transcription factor, controls the expression of genes encoding cytoprotective proteins, including antioxidant enzymes that combat oxidative and electrophilic stress to maintain redox homeostasis. However, recent studies demonstrated that, in cancer, aberrant activation of Nrf2 by epigenetic alterations promotes high expression of cytoprotective proteins, which can decrease the efficacy of anticancer drugs used for chemotherapy. In this review, we summarize recent findings regarding the relationship between oxidative stress, Nrf2, epigenetic modification, and anticancer drug resistance, which should aid in development of new strategies to improve chemotherapeutic efficacy.

• Biomolecules & Therapeutics
• /
• 제26권1호
• /
• pp.69-80
• /
• 2018

Cancer cells reprogram cellular metabolism to support the malignant features of tumors, such as rapid growth and proliferation. The cancer promoting effects of metabolic reprogramming are found in many aspects: generating additional energy, providing more anabolic molecules for biosynthesis, and rebalancing cellular redox states in cancer cells. Metabolic pathways are considered the pipelines to supply metabolic cofactors of epigenetic modifiers. In this regard, cancer metabolism, whereby cellular metabolite levels are greatly altered compared to normal levels, is closely associated with cancer epigenetics, which is implicated in many stages of tumorigenesis. In this review, we provide an overview of cancer metabolism and its involvement in epigenetic modifications and suggest that the metabolic adaptation leading to epigenetic changes in cancer cells is an important non-genetic factor for tumor progression, which cooperates with genetic causes. Understanding the interaction of metabolic reprogramming with epigenetics in cancers may help to develop novel or highly improved therapeutic strategies that target cancer metabolism.

• Molecules and Cells
• /
• 제39권11호
• /
• pp.783-789
• /
• 2016

Afflicted neurons in various neurodegenerative diseases generally display diverse and complex pathological features before catastrophic occurrence of massive neuronal loss at the late stages of the diseases. This complex nature of neuronal pathophysiology inevitably implicates systemwide changes in basic cellular activities such as transcriptional controls and signal cascades, and so on, as a cause. Recently, as one of these systemwide cellular changes associated with neurodegenerative diseases, epigenetic changes caused by protein toxicity have begun to be highlighted. Notably, recent advances in related techniques including next-generation sequencing (NGS) and mass spectrometry enable us to monitor changes in the post-translational modifications (PTMs) of histone proteins and to link these changes in histone PTMs to the specific transcriptional changes. Indeed, epigenetic alterations and consequent changes in neuronal transcriptome are now begun to be extensively studied in neurodegenerative diseases including Alzheimer's disease (AD). In this review, we will discuss details of our current understandings on epigenetic changes associated with two representative neurodegenerative diseases [AD and polyglutamine (polyQ) diseases] and further discuss possible future development of pharmaceutical treatment of the diseases through modulating these epigenetic changes.

• Molecules and Cells
• /
• 제43권4호
• /
• pp.323-330
• /
• 2020

Epigenetic events like DNA methylation and histone modification can alter heritable phenotypes. Zinc is required for the activity of various epigenetic enzymes, such as DNA methyltransferases (DNMTs), histone acetyltransferases (HATs), histone deacetylases (HDACs), and histone demethylases, which possess several zinc binding sites. Thus, the dysregulation of zinc homeostasis can lead to epigenetic alterations. Zinc homeostasis is regulated by Zinc Transporters (ZnTs), Zrt- and Irt-like proteins (ZIPs), and the zinc storage protein metallothionein (MT). Recent advances revealed that ZIPs modulate epigenetics. ZIP10 deficiency was found to result in reduced HATs, confirming its involvement in histone acetylation for rigid skin barrier formation. ZIP13 deficiency, which is associated with Spondylocheirodysplastic Ehlers-Danlos syndrome (SCD-EDS), increases DNMT activity, leading to dysgenesis of dermis via improper gene expressions. However, the precise molecular mechanisms remain to be elucidated. Future molecular studies investigating the involvement of zinc and its transporters in epigenetics are warranted.

• BMB Reports
• /
• 제40권2호
• /
• pp.142-150
• /
• 2007

Epigenetic alterations, represented by aberrant DNA methylation, are deeply involved in human cancers. In gastric cancers, tumor-suppressor genes are inactivated more frequently by promoter methylation than by mutations. We recently showed that H. pylori infection, a potent gastric carcinogenic factor, induces methylation of specific genes in the gastric mucosae. When the methylation levels were analyzed in the gastric mucosae of healthy volunteers, cases with a single gastric cancer, and cases with multiple gastric cancers, who have increasing levels of risks for gastric cancers, there was a significant increasing trend in the methylation levels among the individuals without current H. pylori infection. This finding unequivocally showed the presence of an epigenetic field for cancerization. The degree of the field defect was measured more conveniently using methylation levels of marker genes than using those of tumor-suppressor genes. The presence of an epigenetic field for cancerization has been indicated for liver, colon, Barrett's esophageal, lung, breast, and renal cancers. Since decreased transcription is involved in the specificity of methylated genes, it is likely that specific genes are methylated according to carcinogenic factors. These findings emphasize the usefulness of DNA methylation as a marker for past exposure to carcinogens and future risk of cancer development.