Epigenetic Patterns May Help Identify Schizophrenia Early

Epigenetic aberrations are linked to sporadic breast cancer. Interestingly, certain dietary polyphenols with anti-cancer effects, such as pterostilbene (PTS), have been shown to regulate gene expression by altering epigenetic patterns. Our group has proposed the involvement of DNA methylation and DNA methyltransferase 3B (DNMT3B) as vital players in PTS-mediated suppression of candidate oncogenes and suggested a role of enhancers as target regions. In the present study, we assess a genome-wide impact of PTS on epigenetic marks at enhancers in highly invasive MCF10CA1a breast cancer cells. Following chromatin immunoprecipitation (ChIP)-sequencing in MCF10CA1a cells treated with 7 μM PTS for 9 days, we discovered that PTS leads to increased binding of DNMT3B at enhancers of 77 genes, and 17 of those genes display an overlapping decrease in the occupancy of trimethylation at lysine 36 of histone 3 (H3K36me3), a mark of active enhancers. We selected two genes, PITPNC1 and LINC00910, and found that their enhancers are hypermethylated in response to PTS. These changes coincided with the downregulation of gene expression. Of importance, we showed that 6 out of 17 target enhancers, including PITPNC1 and LINC00910, are bound by an oncogenic transcription factor OCT1 in MCF10CA1a cells. Indeed, the six enhancers corresponded to genes with established or putative cancer-driving functions. PTS led to a decrease in OCT1 binding at those enhancers, and OCT1 depletion resulted in PITPNC1 and LINC00910 downregulation, further demonstrating a role for OCT1 in transcriptional regulation. Our findings provide novel evidence for the epigenetic regulation of enhancer regions by dietary polyphenols in breast cancer cells.

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Intergenerational effects of maternal post-traumatic stress disorder on offspring epigenetic patterns and cortisol levels

Epigenomics ◽

10.2217/epi-2021-0015 ◽

2021 ◽

Author(s):

Line Hjort ◽

Feride Rushiti ◽

Shr-Jie Wang ◽

Peter Fransquet ◽

Sebahate P Krasniqi ◽

...

Keyword(s):

Dna Methylation ◽

Post Traumatic Stress Disorder ◽

Traumatic Stress ◽

Stress Disorder ◽

Post Traumatic Stress ◽

Negative Effects ◽

Significance Levels ◽

Post Traumatic ◽

Cortisol Levels ◽

Epigenetic Patterns

Aim: To investigate the association between maternal post-traumatic stress disorder (PTSD) during pregnancy and offspring DNA methylation and cortisol levels. Materials & methods: Blood genome-wide DNA methylation and cortisol was measured in the youngest child of 117 women who experienced sexual violence/torture during the Kosovo war. Results: Seventy-two percent of women had PTSD symptoms during pregnancy. Their children had higher cortisol levels and differential methylation at candidate genes ( NR3C1, HTR3A and BNDF) . No methylation differences reached epigenome-wide corrected significance levels. Conclusion: Identifying the biological processes whereby the negative effects of trauma are passed across generations and defining groups at high risk is a key step to breaking the intergenerational transmission of the effects of mental disorders.

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Automatic detection of genomic regions with informative epigenetic patterns

BMC Genomics ◽

10.1186/s12864-018-5286-5 ◽

2018 ◽

Vol 19 (1) ◽

Author(s):

Florencio Pazos ◽

Adrian Garcia-Moreno ◽

Juan C. Oliveros

Keyword(s):

Automatic Detection ◽

Genomic Regions ◽

Epigenetic Patterns

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Potential Epigenetic Mechanism(s) Associated With the Persistence of Psychoneurological Symptoms in Women Receiving Chemotherapy for Breast Cancer

Biological Research For Nursing ◽

10.1177/1099800413483545 ◽

2013 ◽

Vol 16 (2) ◽

pp. 160-174 ◽

Cited By ~ 20

Author(s):

Debra Lyon ◽

Lynne Elmore ◽

Noran Aboalela ◽

Jacqueline Merrill-Schools ◽

Nancy McCain ◽

...

Keyword(s):

Breast Cancer ◽

Sleep Disturbances ◽

Alternative Hypothesis ◽

Epigenetic Mechanism ◽

Future Research ◽

Epigenetic Alterations ◽

Inflammatory Activation ◽

Epigenetic Patterns ◽

Psychoneurological Symptoms ◽

Circulating Levels

Due to recent treatment advances, there have been improvements in the proportion of women surviving a diagnosis of breast cancer (BC). However, many of these survivors report persistent adverse side effects following treatment, such as cognitive dysfunction, depressive symptoms, anxiety, fatigue, sleep disturbances, and pain. Investigators have examined circulating levels of inflammatory markers, particularly serum cytokines, for a potential causal relationship to the development/persistence of these psychoneurological symptoms (PNS). While inflammatory activation, resulting from perceived stress or other factors, may directly contribute to the development of PNS, we offer an alternative hypothesis, suggesting that these symptoms are an early step in a cascade of biological changes leading to epigenetic alterations at the level of deoxyribonucleic acid (DNA) methylation, histone modifications, and/or chromatin structure/chromosomal instability. Given that epigenetic patterns have plasticity, if this conjectured relationship between epigenomic/acquired genomic alterations and the development/persistence of PNS is confirmed, it could provide foundational knowledge for future research leading to the recognition of predictive markers and/or treatments to alleviate PNS in women with BC. In this article, we discuss an evolving theory of the biological basis of PNS, integrating knowledge related to inflammation and DNA repair in the context of genetic and epigenetic science to expand the paradigm for understanding symptom acquisition/persistence following chemotherapy.

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Fetal alcohol spectrum disorder (FASD) affects the hippocampal levels of histone variant H2A.Z-2

Biochemistry and Cell Biology ◽

10.1139/bcb-2018-0240 ◽

2019 ◽

Vol 97 (4) ◽

pp. 431-436 ◽

Cited By ~ 3

Author(s):

Taylor L. Gretzinger ◽

Monica Tyagi ◽

Christine J. Fontaine ◽

Manjinder S. Cheema ◽

María González-Perez ◽

...

Keyword(s):

Prenatal Exposure ◽

Fetal Alcohol Spectrum Disorder ◽

Critical Role ◽

Transcriptional Regulators ◽

Histone Variant ◽

Spectrum Disorder ◽

Fetal Alcohol ◽

Rat Pups ◽

Epigenetic Patterns ◽

Fetal Alcohol Spectrum

Fetal alcohol spectrum disorder (FASD) is caused by prenatal exposure to ethanol and has been linked to neurodevelopmental impairments. Alcohol has the potential to alter some of the epigenetic components that play a critical role during development. Previous studies have provided evidence that prenatal exposure to ethanol results in abnormal epigenetic patterns (i.e., hypomethylation) of the genome. The aim of this study was to determine how prenatal exposure to ethanol in rats affects the hippocampal levels of expression of two important brain epigenetic transcriptional regulators involved in synaptic plasticity and memory consolidation: methyl CpG-binding protein 2 (MeCP2) and histone variant H2A.Z. Unexpectedly, under the conditions used in this work we were not able to detect any changes in MeCP2. Interestingly, however, we observed a significant decrease in H2A.Z, accompanied by its chromatin redistribution in both female and male FASD rat pups. Moreover, the data from reverse-transcription qPCR later confirmed that this decrease in H2A.Z is mainly due to down-regulation of its H2A.Z-2 isoform gene expression. Altogether, these data provide strong evidence that prenatal exposure to ethanol alters histone variant H2A.Z during neurogenesis of rat hippocampus.

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Arsenic Biotransformation as a Cancer Promoting Factor by Inducing DNA Damage and Disruption of Repair Mechanisms

Molecular Biology International ◽

10.4061/2011/718974 ◽

2011 ◽

Vol 2011 ◽

pp. 1-11 ◽

Cited By ~ 32

Author(s):

Victor D. Martinez ◽

Emily A. Vucic ◽

Marta Adonis ◽

Lionel Gil ◽

Wan L. Lam

Keyword(s):

Dna Damage ◽

Drinking Water ◽

Repair Process ◽

Dna Methyltransferases ◽

Health Concern ◽

Dna Damage And Repair ◽

Repair Mechanisms ◽

Contaminated Drinking Water ◽

High Concentrations ◽

Epigenetic Patterns

Chronic exposure to arsenic in drinking water poses a major global health concern. Populations exposed to high concentrations of arsenic-contaminated drinking water suffer serious health consequences, including alarming cancer incidence and death rates. Arsenic is biotransformed through sequential addition of methyl groups, acquired from s-adenosylmethionine (SAM). Metabolism of arsenic generates a variety of genotoxic and cytotoxic species, damaging DNA directly and indirectly, through the generation of reactive oxidative species and induction of DNA adducts, strand breaks and cross links, and inhibition of the DNA repair process itself. Since SAM is the methyl group donor used by DNA methyltransferases to maintain normal epigenetic patterns in all human cells, arsenic is also postulated to affect maintenance of normal DNA methylation patterns, chromatin structure, and genomic stability. The biological processes underlying the cancer promoting factors of arsenic metabolism, related to DNA damage and repair, will be discussed here.

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Complex epigenetic patterns in cerebellum generated after developmental exposure to trichloroethylene and/or high fat diet in autoimmune-prone mice

Environmental Science Processes & Impacts ◽

10.1039/c9em00514e ◽

2020 ◽

Vol 22 (3) ◽

pp. 583-594

Author(s):

Sarah J. Blossom ◽

Stepan B. Melnyk ◽

Frank A. Simmen

Keyword(s):

High Fat Diet ◽

Environmental Contaminant ◽

High Fat ◽

Developmental Exposure ◽

Inflammatory Disorders ◽

Immune Mediated ◽

Epigenetic Patterns

Trichloroethylene (TCE) is an environmental contaminant associated with immune-mediated inflammatory disorders and neurotoxicity.

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Genome-Wide DNA Methylation and LncRNA-Associated DNA Methylation in Metformin-Treated and -Untreated Diabetes

Epigenomes ◽

10.3390/epigenomes4030019 ◽

2020 ◽

Vol 4 (3) ◽

pp. 19

Author(s):

Wendy L. Solomon ◽

Stanton B. E. Hector ◽

Shanel Raghubeer ◽

Rajiv T. Erasmus ◽

Andre P. Kengne ◽

...

Keyword(s):

Dna Methylation ◽

Pathway Analysis ◽

Node Of Ranvier ◽

Coupling Factor ◽

Therapeutic Monitoring ◽

Cell Periphery ◽

Genome Wide ◽

Mitochondrial Atp Synthase ◽

Patients With Diabetes ◽

Epigenetic Patterns

Metformin, which is used as a first line treatment for type 2 diabetes mellitus (T2DM), has been shown to affect epigenetic patterns. In this study, we investigated the DNA methylation and potential lncRNA modifications in metformin-treated and newly diagnosed adults with T2DM. Genome-wide DNA methylation and lncRNA analysis were performed from the peripheral blood of 12 screen-detected and 12 metformin-treated T2DM individuals followed by gene ontology (GO) and KEGG pathway analysis. Differentially methylated regions (DMRs) observed showed 22 hypermethylated and 11 hypomethylated DMRs between individuals on metformin compared to screen-detected subjects. Amongst the hypomethylated DMR regions were the SLC gene family, specifically, SLC25A35 and SLC28A1. Fifty-seven lncRNA-associated DNA methylation regions included the mitochondrial ATP synthase-coupling factor 6 (ATP5J). Functional gene mapping and pathway analysis identified regions in the axon initial segment (AIS), node of Ranvier, cell periphery, cleavage furrow, cell surface furrow, and stress fiber. In conclusion, our study has identified a number of DMRs and lncRNA-associated DNA methylation regions in metformin-treated T2DM that are potential targets for therapeutic monitoring in patients with diabetes.

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