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Epigenetics liver

Wen Hao Neo, Christopher A G Booth, Emanuele Azzoni, Lijun Chi, Paul Delgado-Olguín, Marella F T R de Bruijn, Sten Eirik W Jacobsen, Adam J Mead
Despite the well-established cell-intrinsic role of epigenetic factors in normal and malignant hematopoiesis, their cell-extrinsic role remains largely unexplored. Herein we investigated the hematopoietic impact of inactivating Ezh2 , a key component of polycomb repressive complex 2 (PRC2), in the fetal liver (FL) vascular niche. Hematopoietic specific ( Vav -iCre) Ezh2 -inactivation enhanced FL hematopoietic stem cell (HSC) expansion with normal FL erythropoiesis. In contrast, endothelium ( Tie2 -Cre) targeted Ezh2 -inactivation resulted in embryonic lethality with severe anemia at E13...
March 19, 2018: Blood
Maria Giulia Bacalini, Claudio Franceschi, Davide Gentilini, Francesco Ravaioli, Xiaoyuan Zhou, Daniel Remondini, Chiara Pirazzini, Cristina Giuliani, Elena Marasco, Noémie Gensous, Anna Maria Di Blasio, Ewa Ellis, Roberto Gramignoli, Gastone Castellani, Miriam Capri, Stephen Strom, Christine Nardini, Matteo Cescon, Gian Luca Grazi, Paolo Garagnani
The feasibility of liver transplantation from old healthy donors suggests that this organ is able to preserve its functionality during aging. To explore the biological basis of this phenomenon, we characterized the epigenetic profile of liver biopsies collected from 45 healthy liver donors ranging from 13 to 90 years old using the Infinium HumanMethylation450 BeadChip. The analysis indicates that a large remodeling in DNA methylation patterns occurs, with 8823 age-associated differentially methylated CpG probes...
March 15, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Parisa Khodabandeh Shahraki, Yasmin Zare, Negar Azarpira, Massood Hosseinzadeh, Shirin Farjadian
BACKGROUND: Human leukocyte antigen (HLA)-G is a nonclassical HLA class I molecule with modulatory effects on NK and T cells. Because HLA-G expression is frequently detected in different solid tumors, it may be involved in tumor immune evasion. OBJECTIVE: This study was designed to elucidate the prognostic value of HLA-G in hepatocellular carcinoma (HCC) and pancreatic adenocarcinoma (PADC). The influence of hepatitis B virus (HBV) infection on HLA-G expression was also evaluated in patients with HCC...
March 2018: Iranian Journal of Immunology: IJI
Yun Hu, Qinwei Sun, Yan Hu, Zhen Hou, Yibo Zong, Nagmeldin A Omer, Halima Abobaker, Ruqian Zhao
Background: We have shown previously that in ovo betaine injection can prevent nonalcoholic fatty liver induced by glucocorticoid exposure in chickens; yet it remains unknown whether feeding betaine to laying hens may exert similar effects in their progeny. Objective: In this study, we fed laying hens a betaine-supplemented diet, and the progeny were later exposed chronically to corticosterone (CORT) to test hepatoprotective effects and further elucidate underlying mechanisms...
March 1, 2018: Journal of Nutrition
Kedarlal Sharma, JuhiSingh, Emma E Frost, Prakash P Pillai
MethylCpG binding protein-2 (MeCP2) is an epigenetic regulator and essential for brain development.MeCP2 mutations are associated with a spectrum of neuro-developmental disorders that vary depending on the patient gender, most notably Rett Syndrome. MeCP2 is essential for normal neuronal maturation, and glial cell function in the brain. Besides, its role in neurodevelopmental disorders, MeCP2 is involved in many cancers such as breast, colorectal, lung, liver, and prostate cancer. Glioma is the most lethal form of brain cancer...
March 11, 2018: Neuroscience Letters
Hemant Gujar, Jane W Liang, Nicholas C Wong, Khyobeni Mozhui
The Illumina Infinium MethylationEPIC provides an efficient platform for profiling DNA methylation in humans at over 850,000 CpGs. Model organisms such as mice do not currently benefit from an equivalent array. Here we used this array to measure DNA methylation in mice. We defined probes targeting conserved regions and performed differential methylation analysis and compared between the array-based assay and affinity-based DNA sequencing of methyl-CpGs (MBD-seq) and reduced representation bisulfite sequencing...
2018: PloS One
Sobha Puppala, Cun Li, Jeremy P Glenn, Romil Saxena, Samer Gawrieh, Amy Quinn, Jennifer Palarczyk, Edward J Dick, Peter W Nathanielsz, Laura A Cox
Maternal obesity (MO) increases offspring cardiometabolic disease risk. Altered fetal liver development in response to the challenge of MO has metabolic consequences underlying adverse offspring life-course health outcomes. Little is known about molecular pathways and potential epigenetic changes regulating primate fetal liver responses to MO. We hypothesized that MO would induce fetal baboon liver epigenetic changes resulting in dysregulation of key metabolic pathways that impact lipid metabolism. MO was induced prior to pregnancy by a high fat, high sucrose diet...
March 7, 2018: Journal of Physiology
Alexander Beck, Franziska Trippel, Alexandra Wagner, Saskia Joppien, Max Felle, Christian Vokuhl, Thomas Schwarzmayr, Tim M Strom, Dietrich von Schweinitz, Gernot Längst, Roland Kappler
Background: Hepatoblastoma (HB) is the most common liver tumor of childhood and occurs predominantly within the first 3 years of life. In accordance to its early manifestation, HB has been described to display an extremely low mutation rate. As substitute, epigenetic modifiers seem to play an exceptional role in its tumorigenesis, which holds promise to develop targeted therapies and establish biomarkers for patient risk stratification. Results: We examined the role of a newly described protein complex consisting of three epigenetic regulators, namely E3 ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), ubiquitin-specific-processing protease 7 (USP7), and DNA methyltransferase 1 (DNMT1), in HB...
2018: Clinical Epigenetics
Jarno E J Wolters, Simone G J van Breda, Jonas Grossmann, Claudia Fortes, Florian Caiment, Jos C S Kleinjans
We performed a multiple 'omics study by integrating data on epigenomic, transcriptomic, and proteomic perturbations associated with mitochondrial dysfunction in primary human hepatocytes caused by the liver toxicant valproic acid (VPA), to deeper understand downstream events following epigenetic alterations in the mitochondrial genome. Furthermore, we investigated persistence of cross-omics changes after terminating drug treatment. Upon transient methylation changes of mitochondrial genes during VPA-treatment, increasing complexities of gene-interaction networks across time were demonstrated, which normalized during washout...
February 28, 2018: Toxicology Letters
Saravana Kumar Kailasam Mani, Ourania Andrisani
Chronic Hepatitis B Virus (HBV) infection is linked to hepatocellular carcinoma (HCC) pathogenesis. Despite the availability of a HBV vaccine, current treatments for HCC are inadequate. Globally, 257 million people are chronic HBV carriers, and children born from HBV-infected mothers become chronic carriers, destined to develop liver cancer. Thus, new therapeutic approaches are needed to target essential pathways involved in HCC pathogenesis. Accumulating evidence supports existence of hepatic cancer stem cells (hCSCs), which contribute to chemotherapy resistance and cancer recurrence after treatment or surgery...
March 2, 2018: Genes
Cajsa Davegårdh, Sonia García-Calzón, Karl Bacos, Charlotte Ling
BACKGROUND: Type 2 diabetes (T2D) is a multifactorial, polygenic disease caused by impaired insulin secretion and insulin resistance. Genome-wide association studies (GWAS) were expected to resolve a large part of the genetic component of diabetes; yet, the single nucleotide polymorphisms identified by GWAS explain less than 20% of the estimated heritability for T2D. There was subsequently a need to look elsewhere to find disease-causing factors. Mechanisms mediating the interaction between environmental factors and the genome, such as epigenetics, may be of particular importance in the pathogenesis of T2D...
February 7, 2018: Molecular Metabolism
Dirk Walter, Patrick N Harter, Florian Battke, Ria Winkelmann, Markus Schneider, Katharina Holzer, Christine Koch, Jörg Bojunga, Stefan Zeuzem, Martin Leo Hansmann, Jan Peveling-Oberhag, Oliver Waidmann
Data on intratumoral heterogeneity of small intestine neuroendocrine tumors (SI-NETs) and related liver metastasis are limited. The aim of this study was to characterize genetic heterogeneity of 5 patients with SI-NETs. Therefore, formalin-fixed, paraffin-embedded tissue samples of primary and metastatic lesions as well as benign liver of five patients with synchronously metastasized, well differentiated SI-NETs were analyzed with whole exome sequencing. For one patient, chip based 850k whole DNA methylome analysis was performed of primary and metastatic tumor tissue as well as control tissue...
February 28, 2018: Scientific Reports
Xiaonan Ji, Yayu Xue, Yu Wu, Fang Feng, Xiangdong Gao
BACKGROUND: Hepatocellular carcinoma (HCC) is a product of cumulative genetic, epigenetic, somatic, and endocrine aberrations. Identifying the differentially expressed genes (DEGs) in HCC is of critical importance for diagnosis and treatment. The purpose of the present study was to screen the key genes associated with hepatocellular carcinoma and to investigate the functions underlying hepatocellular carcinoma progression. MATERIALS AND METHODS: The gene expression profile of GSE64041, GSE40367 and GSE60502, including 100 specimens from HCC patients and 92 specimens from normal liver controls, was downloaded from the GEO database...
December 30, 2017: Pathology, Research and Practice
Sarah Jean Glastras, Hui Chen, Carol A Pollock, Sonia Saad
Obesity, together with insulin resistance, promotes multiple metabolic abnormalities and is strongly associated with an increased risk of chronic disease including type 2 diabetes (T2D), hypertension, cardiovascular disease, non-alcoholic fatty liver disease and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all different stages of the lifespan. Importantly, the proportion of women of reproductive age who are overweight or obese is increasing at an alarming rate and has potential ramifications for offspring health and disease risk...
February 26, 2018: Bioscience Reports
Joanna Nowacka-Woszuk, Izabela Szczerbal, Anna M Malinowska, Agata Chmurzynska
Dietary triggers acting on a developing fetus can affect the functioning of the body in later life; this can be observed on various levels, including epigenetic modifications and gene expression. Early-life programmed changes may be transmitted to successive generations. In this study, the impact of prenatal restricted diet was studied in four generations of rats. We hypothesized that this diet can induce changes in the expression of major genes involved in two epigenetic mechanisms: DNA methylation and histone modifications...
2018: PloS One
Ryan A Hlady, Keith D Robertson
Hepatocellular carcinoma (HCC) is the most prevalent primary tumor of the liver, and is steadily becoming one of the most lethal cancers worldwide. Liver resection, which is the recommended procedure for early localized HCC, results in frequent recurrence (50-70%), while the standard of care for late-stage HCC, multikinase inhibitors, only improves survival by a few months. The lack of success for these treatment modalities is attributable, at least in part, to marked phenotypic heterogeneity within the tumor...
February 2018: Seminars in Liver Disease
Zhen Hou, Qinwei Sun, Yun Hu, Shu Yang, Yibo Zong, Ruqian Zhao
As a feed additive, betaine is widely used in livestock production for its ability to promote growth. Our previous studies had reported that maternal betaine supplementation altered hepatic metabolism in offspring. But it remains unknown whether and how maternal betaine modulates metabolism of thyroid hormones in the offspring chickens by epigenetic modification. In this study, one hundred and twenty Rugao yellow-feathered laying hens were randomly divided into two groups, and were fed basal diet with or without 0...
February 13, 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Madeline Rose Keleher, Rabab Zaidi, Shyam Shah, M Elsa Oakley, Cassondra Pavlatos, Samir El Idrissi, Xiaoyun Xing, Daofeng Li, Ting Wang, James M Cheverud
We investigated maternal obesity in inbred SM/J mice by assigning females to a high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males, cross-fostering the offspring to low-fat-fed SM/J nurses at birth, and weaning the offspring onto a high-fat or low-fat diet. A maternal high-fat diet exacerbated obesity in the high-fat-fed daughters, causing them to weigh more, have more fat, and have higher serum levels of leptin as adults, accompanied by dozens of gene expression changes and thousands of DNA methylation changes in their livers and hearts...
2018: PloS One
Kaja H Skjærven, Lars Martin Jakt, Jorge M O Fernandes, John Arne Dahl, Anne-Catrin Adam, Johanna Klughammer, Christoph Bock, Marit Espe
Micronutrient status of parents can affect long term health of their progeny. Around 2 billion humans are affected by chronic micronutrient deficiency. In this study we use zebrafish as a model system to examine morphological, molecular and epigenetic changes in mature offspring of parents that experienced a one-carbon (1-C) micronutrient deficiency. Zebrafish were fed a diet sufficient, or marginally deficient in 1-C nutrients (folate, vitamin B12, vitamin B6, methionine, choline), and then mated. Offspring livers underwent histological examination, RNA sequencing and genome-wide DNA methylation analysis...
February 14, 2018: Scientific Reports
Xunmei Yuan, Kazutaka Tsujimoto, Koshi Hashimoto, Kenichi Kawahori, Nozomi Hanzawa, Miho Hamaguchi, Takami Seki, Makiko Nawa, Tatsuya Ehara, Yohei Kitamura, Izuho Hatada, Morichika Konishi, Nobuyuki Itoh, Yoshimi Nakagawa, Hitoshi Shimano, Takako Takai-Igarashi, Yasutomi Kamei, Yoshihiro Ogawa
The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α-dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood...
February 12, 2018: Nature Communications
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