• BMB Reports
• /
• v.43 no.10
• /
• pp.649-655
• /
• 2010

Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disorder and shows progressive memory loss and cognitive decline. Intraneuronal filaments composed of aggregated hyperphosphorylated tau protein, called neurofibrillary tangles, along with extracellular accumulations of amyloid $\beta$ protein (A$\beta$), called senile plaques, are known to be the neuropathological hallmarks of AD. In light of recent studies, epigenetic modification has emerged as one of the pathogenic mechanisms of AD. Epigenetic changes encompass an array of molecular modifications to both DNA and chromatin, including transcription factors and cofactors. In this review, we summarize how DNA methylation and changes to DNA chromatin packaging by post-translational histone modification are involved in AD. In addition, we describe the role of SIRTs, histone deacetylases, and the effect of SIRT-modulating drugs on AD. Lastly, we discuss how amyloid precursor protein (APP) intracellular domain (AICD) regulates neuronal transcription. Our understanding of the epigenomes and transcriptomes of AD may warrant future identification of novel biological markers and beneficial therapeutic targets for AD.

• Toxicological Research
• /
• v.31 no.1
• /
• 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.

• Toxicological Research
• /
• v.33 no.1
• /
• 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.

• Journal of Environmental Health Sciences
• /
• v.35 no.5
• /
• pp.343-354
• /
• 2009

Since Barker found associations between low birth weight and several chronic diseases later in life, the hypothesis of fetal origins of adult disease (aka, Barker Hypothesis) and epigenetics have been emerging as a new paradigm for geneenvironment interaction of chronic disease. Epigenetics is the study of heritable changes in gene silencing that occur without any change in DNA sequence. Gene expression can be regulated by several epigenetic mechanisms, including DNA methylation and histone modifications, which may be associated with chronic conditions, such as cancers, cardiovascular disease, and type-2 diabetes. One carbon metabolism which involves the transfer of a methyl group catalyzed by DNA methyltransferase is an important mechanism by which DNA methylation occurs in promoter regions and/or repetitive elements of the genome. Environmental factors may induce epigenetic modification through production of reactive oxygen species, alteration of methyltransferase activity, and/or interference with methyl donors. In this review, we introduce recent studies of epigenetic modification and environmental factors, such as heavy metals, environmental hormones, air pollution, diet and psychosocial stress. We also discuss epigenetic perspectives of early life environmental exposure and late life disease occurrence.

• Animal cells and systems
• /
• v.12 no.3
• /
• pp.117-125
• /
• 2008

One of the interesting trends in genome research is the study about epigenetic modification above single gene level. Epigenetics refers study about heritable change in the genome, which accompany modification in DNA or Chromatin besides DNA sequence alteration. We used to have the idea that the coding potential of the genome lies within the arrangement of the four bases A, T, G, C; However, additional information that affects phenotype is stored in the distribution of the modified base 5-methylcytosine. This form of information storage is flexible enough to be adapted for different somatic cell types, yet is stable enough to be retained during mitosis and/or meiosis. Epigenetic modification is a modification of the genome, as opposed to being part of the genome, so is known as "epigenetics"(Greek for "upon" genetics). This modification could be methylation on Cytosine base or post translational modification on histone protein(methylation, acetylation, phosphorylation, Sumoylation)($Dimitrijevi\hat{E}$ et al 2005). In this review, we would like to focus on the relationship of DNA methylation and cancer.

• The Journal of the Korea Contents Association
• /
• v.13 no.8
• /
• pp.466-473
• /
• 2013

Gene expression is regulated by a wide range of mechanisms at the DNA sequence level. In addition, gene expression is also regulated by epigenetic mechanisms through DNA methylation, histone modification, and ncRNA. To understand the regulation of gene expression at the epigenetic level, we constructed aging related gene database and analyzed epigenetic properties that are focused on DNA methylation. The DNA methylation of promoter or upstream region of the genes induces to repress the gene expression. We compared and analyzed distribution between whole human genes and aging related genes in the epigenetic properties such as CGI distribution, methylation motif pattern, and TFBS (transcription factor binding site) distribution. In contrast to methylation motif pattern, CGI and TFBS distributions are positively correlated with epigenetic regulation of aging related gene expression. In this study, the epigenetic data about DNA methylation of the aging genes will provide us to understand phenomena of the aging and epigenetic mechanism for regulation of aging related genes.

• Journal of Life Science
• /
• v.28 no.12
• /
• pp.1536-1544
• /
• 2018

Depression is a common, serious, and recurring mental disorder. The pathogenesis of depression involves many factors such as environmental factor, genetic factor and alteration of structure and function in neurobiological systems. Increasing evidence supports that epigenetic alteration may be associated with depression. The epigenetics is explained as the mechanisms by which environmental factor causes changes in chromatin structure and alters gene expression without changing DNA base sequence. DNA methylation and histone modification involving histone acetylation and methylation are the main epigenetic mechanisms. Animal studies have shown that stressful environment such as early life stress can leave persistent epigenetic marks in the genome, which alter gene expression and influence neural and behavioral function through adulthood. A potentially important gene in depression is brain-derived neurotrophic factor (BDNF). BDNF plays a central role in depression and antidepressant action. In studies of the rodent, exposure to stress at prenatal, postnatal, and adult stages alters BDNF expression through histone modification and DNA methylation of the BDNF gene which results in anxiety and depressive-like behavior. This review discusses recent advances in the study of the epigenetic mechanisms that contribute to depression, particularly histone modification and DNA methylation of the BDNF gene, that may help in the development of new targets for depression treatment.

• Molecules and Cells
• /
• v.38 no.8
• /
• pp.677-684
• /
• 2015

Osteoarthritis (OA) is one of the most prevalent forms of joint disorder, associated with a tremendous socioeconomic burden worldwide. Various non-genetic and lifestyle-related factors such as aging and obesity have been recognized as major risk factors for OA, underscoring the potential role for epigenetic regulation in the pathogenesis of the disease. OA-associated epigenetic aberrations have been noted at the level of DNA methylation and histone modification in chondrocytes. These epigenetic regulations are implicated in driving an imbalance between the expression of catabolic and anabolic factors, leading eventually to osteoarthritic cartilage destruction. Cellular senescence and metabolic abnormalities driven by OA-associated risk factors appear to accompany epigenetic drifts in chondrocytes. Notably, molecular events associated with metabolic disorders influence epigenetic regulation in chondrocytes, supporting the notion that OA is a metabolic disease. Here, we review accumulating evidence supporting a role for epigenetics in the regulation of cartilage homeostasis and OA pathogenesis.

• Animal cells and systems
• /
• v.16 no.1
• /
• pp.1-10
• /
• 2012

Most living organisms synchronize their physiological and behavioral activities with the daily changes in the environment using intrinsic time-keeping systems called circadian clocks. In mammals, the key molecular features of the internal clock are transcription- and translational-based negative feedback loops, in which clock-specific transcription factors activate the periodic expression of their own repressors, thereby generating the circadian rhythms. CLOCK and BMAL1, the basic helix-loop-helix (bHLH)/PAS transcription factors, constitute the positive limb of the molecular clock oscillator. Recent investigations have shown that various levels of posttranslational regulation work in concert with CLOCK/BMAL1 in mediating circadian and cellular stimuli to control and reset the circadian rhythmicity. Here we review how the CLOCK and BMAL1 activities are regulated by intracellular distribution, posttranslational modification, and the recruitment of various epigenetic regulators in response to circadian and cellular signaling pathways.

• Food Science and Industry
• /
• v.50 no.1
• /
• 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