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Christian Heck, Yael Michaeli, Ilko Bald, Yuval Ebenstein
The field of epigenetics describes the relationship between genotype and phenotype, by regulating gene expression without changing the canonical base sequence of DNA. It deals with molecular genomic information that is encoded by a rich repertoire of chemical modifications and molecular interactions. This regulation involves DNA, RNA and proteins that are enzymatically tagged with small molecular groups that alter their physical and chemical properties. It is now clear that epigenetic alterations are involved in development and disease, and thus, are the focus of intensive research...
October 13, 2018: Current Opinion in Biotechnology
Shufen Li, Qiong Yang, Yu Hou, Tingyun Jiang, Lu Zong, Zhongju Wang, Xia Luo, Wenquan Liang, Hu Zhao, Yuping Ning, Cunyou Zhao
Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental illnesses with evidence of significant genetic and environmental etiological elements in their complex etiologies. 5'-Methylcytosine is the main epigenetic DNA modification that mediates the interplay between genetic and environmental components. In humans, most 5'-methylcytosine modifications are observed in CpG-rich regions within the long interspersed nuclear element (LINE-1). LINE-1 is a mobile retrotransposon that comprises ∼17% of the human genome, and its methylation levels are highly correlated with global DNA methylation levels...
October 10, 2018: Journal of Psychiatric Research
Deirdre M McCarthy, Thomas J Morgan, Sarah E Lowe, Matthew J Williamson, Thomas J Spencer, Joseph Biederman, Pradeep G Bhide
Use of tobacco products is injurious to health in men and women. However, tobacco use by pregnant women receives greater scrutiny because it can also compromise the health of future generations. More men smoke cigarettes than women. Yet the impact of nicotine use by men upon their descendants has not been as widely scrutinized. We exposed male C57BL/6 mice to nicotine (200 μg/mL in drinking water) for 12 wk and bred the mice with drug-naïve females to produce the F1 generation. Male and female F1 mice were bred with drug-naïve partners to produce the F2 generation...
October 2018: PLoS Biology
Hui Cheng, Yutian Wang, Jian Zhang, Sheng Zhang, Xiaoling Ma, Xinglan An, Xiaxia Man, Xueming Zhang, Ziyi Li, Bo Tang
PRDM14, a member of the PRDM family protein, plays an important role in the regulation of epigenetic reprogramming. Knockdown of Prdm14 in germ cells can lead to female and male subfertility, and the function of PRDM14 appears to be conserved across mammalian species. Thus, we analyzed the expression of Prdm14 in parthenogenetic embryos at all stages of preimplantation and then evaluated the effect of Prdm14 downregulation on porcine parthenogenetic embryonic development. We found that Prdm14 transcripts are highly expressed in the metaphase II (MII) oocyte, and their level gradually increased from the 2-cell to 8-cell stage and slightly declined at the blastocyst stage during the development of parthenogenetic porcine embryos...
October 16, 2018: Cellular Reprogramming
Schapoor Hessam, Thilo Gambichler, Marina Skrygan, Michael Sand, Ines Rüddel, Lisa Scholl, Falk G Bechara
BACKGROUND: As environmental factors appear to predispose patients to hidradenitis suppurativa (HS), studying epigenetic modifications is of interest to further understand the pathogenesis of HS. OBJECTIVES: To study the expression of DNA hydroxymethylation regulators, namely the ten-eleven translocation (TET) and isocitrate dehydrogenase (IDH) family, in the skin of HS patients. MATERIALS & METHODS: Twenty patients with HS and 12 healthy subjects were recruited...
October 15, 2018: European Journal of Dermatology: EJD
Joel Hrit, Leeanne Goodrich, Cheng Li, Bang-An Wang, Ji Nie, Xiaolong Cui, Elizabeth Allene Martin, Eric Simental, Jenna Fernandez, Monica Y Liu, Joseph R Nery, Rosa Castanon, Rahul M Kohli, Natalia Tretyakova, Chuan He, Joseph R Ecker, Mary Goll, Barbara Panning
TET enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine and higher oxidized derivatives. TETs stably associate with and are post-translationally modified by the nutrient-sensing enzyme OGT, suggesting a connection between metabolism and the epigenome. Here, we show for the first time that modification by OGT enhances TET1 activity in vitro. We identify a TET1 domain that is necessary and sufficient for binding to OGT and report a point mutation that disrupts the TET1-OGT interaction. We show that this interaction is necessary for TET1 to rescue hematopoetic stem cell production in tet mutant zebrafish embryos, suggesting that OGT promotes TET1's function during development...
October 16, 2018: ELife
Sadegh Fattahi, Monireh Golpour, Fatemeh Amjadi-Moheb, Marzieh Sharifi-Pasandi, Parastesh Khodadadi, Maryam Pilehchian-Langroudi, Gholam Hossein Ashrafi, Haleh Akhavan-Niaki
Gastric cancer is a major health problem worldwide occupying most frequent causes of cancer-related mortality. In addition to genetic modifications, epigenetic alterations catalyzed by DNA methyltransferases (DNMTs) are a well-characterized epigenetic hallmark in gastric cancer. The reversible nature of epigenetic alterations and central role of DNA methylation in diverse biological processes provides an opportunity for using DNMT inhibitors to enhance the efficacy of chemotherapeutics. In this review, we discussed key factors or mechanisms such as SNPs, infections and genetic modifications that trigger DNMTs level modification in gastric cancer, and their potential roles in cancer progression...
October 16, 2018: Epigenomics
Jacopo Agrimi, Carlotta Baroni, Ekene Anakor, Vincenzo Lionetti
The number of obese patients undergoing cardiac and non cardiac surgery is rapidly increasing because they are more prone to concomitant diseases, such as diabetes, thrombosis, sleep-disordered breathing, cardiovascular and cerebrovascular diseases. Even if guidelines are already available to manage anesthesia and surgery of obese patients, the assessment of the perioperative morbidity and mortality from heart and brain disorders in morbidly obese surgical patients will be challenging in the next years. The present review will recapitulate the new mechanisms underlying the heart-brain axis vulnerability during the perioperative period in morbidly obese patients...
October 15, 2018: Current Medicinal Chemistry
Sylvia E Badon, Alyson J Littman, Kwun Chuen Gary Chan, Mahlet G Tadesse, Patricia L Stapleton, Theo K Bammler, Tanya K Sorensen, Michelle A Williams, Daniel A Enquobahrie
AIM: Investigate associations of leisure time physical activity (LTPA) with DNA methylation and miRNAs during pregnancy. Patients & methods: LTPA, candidate DNA methylation and circulating miRNAs were measured (average 15 weeks gestation) in pregnant women (n = 92). RESULTS: Each additional hour of prepregnancy LTPA duration was associated with hypermethylation in C1orf212 (β = 0.137, 95% CI: 0.004-0.270) and higher circulating miR-146b-5p (β = 0.084, 95% CI: 0...
October 16, 2018: Epigenomics
Hernán Guillermo Hernández, Adrián Gabriel Sandoval-Hernández, Pablo Garrido-Gil, José Luis Labandeira-Garcia, María Victoria Zelaya, Gustavo F Bayon, Agustín F Fernández, Mario F Fraga, Gonzalo Arboleda, Humberto Arboleda
OBJECTIVE: To study DNA methylation patterns of cortical pyramidal layers susceptible to late-onset Alzheimer's disease (LOAD) neurodegeneration. METHODS: Laser-assisted microdissection to select pyramidal layers' cells in frontal cortex of 32 human brains (18 LOAD) and Infinium DNA Methylation 450K analysis were performed to find differential methylated positions and regions, in addition to the corresponding gene set functional enrichment analyses. RESULTS: Differential hypermethylation in several genomic regions and genes mainly in HOXA3, GSTP1, CXXC1-3 and BIN1...
October 16, 2018: Epigenomics
Yamei Pang, Jian Liu, Xiang Li, Guodong Xiao, Huangzhen Wang, Ganghua Yang, Yanbo Li, Shou-Ching Tang, Sida Qin, Ning Du, Henggang Zhang, Dapeng Liu, Xin Sun, Hong Ren
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with a poor prognosis. The microRNA-200 (miR-200) family has been associated with breast cancer metastasis. However, the epigenetic mechanisms underlying miR-200b repression in TNBC are not fully elucidated. In this study, we found that MYC proto-oncogene, bHLH transcription factor (MYC) and DNA methyltransferase 3A (DNMT3A) were highly expressed in TNBC tissues compared with other breast cancer subtypes, while miR-200b expression was inhibited significantly...
October 16, 2018: Journal of Cellular and Molecular Medicine
Laurent Jutras-Dubé, Adrien Henry, Paul François
Theoretical and computational modelling are crucial to understand dynamics of embryonic development. In this tutorial chapter, we describe two models of gene networks performing time-dependent acquisition of positional information under control of a dynamic morphogen: a toy-model of a bistable gene under control of a morphogen, allowing for the numerical computation of a simple Waddington's epigenetic landscape, and a recently published model of gap genes in Tribolium under control of multiple enhancers. We present detailed commented implementations of the models using python and jupyter notebooks...
2018: Methods in Molecular Biology
Chang-Wei Wei, Ting Luo, Shan-Shan Zou, An-Shi Wu
Long noncoding RNAs (lncRNAs) refer to a group of noncoding RNAs (ncRNAs) that has a transcript of more than 200 nucleotides in length in eukaryotic cells. The lncRNAs regulate gene expression at epigenetic, transcriptional, and post-transcriptional levels by multiple action modes. In this review, we describe the diverse roles reported for lncRNAs, and discuss how they could mechanistically be involved in the development of central nervous system (CNS) and neurodegenerative diseases. Further studies on the function of lncRNAs and their mechanism will help deepen our understanding of the development, function, and diseases of the CNS, and provide new ideas for the design and development of some therapeutic drugs...
2018: Frontiers in Behavioral Neuroscience
Irene Lacal, Rossella Ventura
Parents' stressful experiences can influence an offspring's vulnerability to many pathological conditions, including psychopathologies, and their effects may even endure for several generations. Nevertheless, the cause of this phenomenon has not been determined, and only recently have scientists turned to epigenetics to answer this question. There is extensive literature on epigenetics, but no consensus exists with regard to how and what can (and must) be considered to study and define epigenetics processes and their inheritance...
2018: Frontiers in Molecular Neuroscience
Jyotirmaya Behera, Kimberly E Kelly, Michael J Voor, Naira Metreveli, Suresh C Tyagi, Neetu Tyagi
Previously, we have shown hyperhomocysteinemia (HHcy) to have a detrimental effect on bone remodeling, which is associated with osteoporosis. During transsulfuration, Hcy is metabolized into hydrogen sulfide (H2 S), a gasotransmitter molecule known to regulate bone formation. Therefore, in the present study, we examined whether H2 S ameliorates HHcy induced epigenetic and molecular alterations leading to osteoporotic bone loss. To test this mechanism, we employed cystathionine-beta-synthase heterozygote knockout mice, fed with a methionine rich diet (CBS+/- +Met), supplemented with H2 S-donor NaHS for 8 weeks...
October 15, 2018: Scientific Reports
Raquel L Costa, Mariana Boroni, Marcelo A Soares
The human papillomavirus (HPV) is present in a significant fraction of head-and-neck squamous cell cancer (HNSCC). The main goal of this study was to identify distinct co-expression patterns between HPV+ and HPV- HNSCC and to provide insights into potential regulatory mechanisms/effects within the analyzed networks. We selected cases deposited in The Cancer Genome Atlas database comprising data of gene expression, methylation profiles and mutational patterns, in addition to clinical information. The intersection among differentially expressed and differentially methylated genes showed the negative correlations between the levels of methylation and expression, suggesting that these genes have their expression levels regulated by methylation alteration patterns in their promoter...
October 15, 2018: Scientific Reports
Viviane Rostirola Elsner, Laura Reck Cechinel, Louisiana Carolina Ferreira de Meireles, Karine Bertoldi, Ionara Rodrigues Siqueira
Although the involvement of gender in epigenetic machinery in peripheral tissues during the neonatal period has been suggested, the gender-related epigenetic profile of brain areas during the adolescent period is rarely exploited. Furthermore, the influence of time of day on hippocampal acetylation marks has been demonstrated in young adult and aged rats; however, there are no studies reporting epigenetic changes in the adolescent period. Therefore, this study aimed to investigate the effects of gender on hippocampal DNA methyltransferase 1 content and histone deacetylase (HDAC) activity of adolescent rats at different time points, specifically early morning and afternoon...
December 2018: Neural Regeneration Research
Sergei V Fedorovich, Polina P Voronina, Tatyana V Waseem
Glucose is the main energy substrate for neurons, however, at certain conditions, e.g. in starvation, these cells could also use ketone bodies. This approach is used in clinical conditions as the ketogenic diet. The ketogenic diet is actually a biochemical model of fasting. It includes replacing carbohydrates by fats in daily meal. Synthesis of ketone bodies β-hydroxubutirate, acetoacetate and acetone begins once glycogen stores have depleted in the liver. The ketogenic diet can be used to treat clinical conditions, primarily epilepsy...
December 2018: Neural Regeneration Research
Norbert O Reich, Eric Dang, Martin Kurnik, Sarath Pathuri, Clayton B Woodcock
Two DNA methyltransferases, Dam and β-class cell cycle-regulated DNA methyltransferase (CcrM), are key mediators of bacterial epigenetics. CcrM from Caulobacter crescentus (CcrM C. crescentus, methylates adenine at 5'GANTC3') displays 105-107 fold  discrimination against non-cognate sequences. However, the underlying recognition mechanism is unclear. Here, CcrM C. crescentus activity was either improved or mildly attenuated with substrates having one to three mismatched base pairs within or adjacent to the recognition site, but only if the strand undergoing methylation is left unchanged...
October 15, 2018: Journal of Biological Chemistry
Dora L Costa, Noelle Yetter, Heather DeSomer
We study whether paternal trauma is transmitted to the children of survivors of Confederate prisoner of war (POW) camps during the US Civil War (1861-1865) to affect their longevity at older ages, the mechanisms behind this transmission, and the reversibility of this transmission. We examine children born after the war who survived to age 45, comparing children whose fathers were non-POW veterans and ex-POWs imprisoned in very different camp conditions. We also compare children born before and after the war within the same family by paternal ex-POW status...
October 15, 2018: Proceedings of the National Academy of Sciences of the United States of America
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