Epigenetic modifications in the biology of nonalcoholic fatty liver disease: The role of DNA hydroxymethylation and TET proteins

The 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification whose role in the pathogenesis of metabolic-related complex diseases remains unexplored; 5-hmC appears to be prevalent in the mitochondrial genome. The Ten-Eleven-Translocation (TET) family of proteins is responsible for catalyzing th...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autor principal: Pirola, C.J
Otros Autores: Scian, R., Gianotti, T.F, Dopazo, H., Rohr, C., Martino, J.S, Castaño, G.O, Sookoian, S.
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Lippincott Williams and Wilkins 2015
Acceso en línea:Registro en Scopus
DOI
Handle
Registro en la Biblioteca Digital
Aporte de:Registro referencial: Solicitar el recurso aquí
LEADER 15286caa a22018737a 4500
001 PAPER-24876
003 AR-BaUEN
005 20230518205649.0
008 190411s2015 xx ||||fo|||| 00| 0 eng|d
024 7 |2 scopus  |a 2-s2.0-84941686246 
024 7 |2 cas  |a 5 hydroxymethylcytosine, 1123-95-1; cytosine, 71-30-7; 5-hydroxymethylcytosine; Cytosine; DNA-Binding Proteins; Heat-Shock Proteins; PPARGC1A protein, human; Proto-Oncogene Proteins; TET1 protein, human; Transcription Factors 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a MEDIA 
100 1 |a Pirola, C.J. 
245 1 0 |a Epigenetic modifications in the biology of nonalcoholic fatty liver disease: The role of DNA hydroxymethylation and TET proteins 
260 |b Lippincott Williams and Wilkins  |c 2015 
270 1 0 |m Pirola, C.J.; Instituto de Investigaciones Médicas A. Lanari, CONICET, Combatiente de Malvinas 3150, Argentina 
506 |2 openaire  |e Política editorial 
504 |a Loomba, R., Sanyal, A.J., The global NAFLD epidemic (2013) Nat Rev Gastroenterol Hepatol., 10, pp. 686-690 
504 |a Sookoian, S., Pirola, C.J., Non-alcoholic fatty liver disease is strongly associated with carotid atherosclerosis: A systematic review (2008) J Hepatol., 49, pp. 600-607 
504 |a Targher, G., Day, C.P., Bonora, E., Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease (2010) N Engl J Med., 363, pp. 1341-1350 
504 |a Targher, G., Byrne, C.D., Clinical review: Nonalcoholic fatty liver disease: A novel cardiometabolic risk factor for type 2 diabetes and its complications (2013) J Clin Endocrinol Metab., 98, pp. 483-495 
504 |a Tarantino, G., Finelli, C., What about non-alcoholic fatty liver disease as a new criterion to define metabolic syndrome (2013) World J Gastroenterol, 19, pp. 3375-3384 
504 |a Sookoian, S., Rosselli, M.S., Gemma, C., Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: Impact of liver methylation of the peroxisome proliferator-activated receptor gamma coactivator 1alpha promoter (2010) Hepatology., 52, pp. 1992-2000 
504 |a Brunt, E.M., Pathology of fatty liver disease (2007) Mod Pathol., 20, pp. S40-S48 
504 |a Brunt, E.M., Histopathology of non-alcoholic fatty liver disease (2009) Clin Liver Dis., 13, pp. 533-544 
504 |a Fierbinteanu-Braticevici, C., Negreanu, L., Tarantino, G., Is fatty liver always benign and should not consequently be treated (2013) J Physiol Pharmacol, 64, pp. 3-9 
504 |a Singh, S., Allen, A.M., Wang, Z., Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: A systematic review and meta-analysis of paired-biopsy studies (2015) Clin Gastroenterol Hepatol., 13, pp. 643-654 
504 |a Torres, D.M., Harrison, S.A., Nonalcoholic fatty liver disease: Fibrosis portends a worse prognosis (2015) Hepatology., 61, pp. 1462-1464 
504 |a Sookoian, S., Pirola, C.J., The genetic epidemiology of nonalcoholic fatty liver disease: Toward a personalized medicine (2012) Clin Liver Dis., 16, pp. 467-485 
504 |a Ahrens, M., Ammerpohl, O., Von Schönfels, W., DNA methylation analysis in nonalcoholic fatty liver disease suggests distinct diseasespecific and remodeling signatures after bariatric surgery (2013) Cell Metab., 18, pp. 296-302 
504 |a Murphy, S.K., Yang, H., Moylan, C.A., Relationship between methylome and transcriptome in patients with nonalcoholic fatty liver disease (2013) Gastroenterology., 145, pp. 1076-1087 
504 |a Pirola, C.J., Gianotti, T.F., Burgueno, A.L., Epigenetic modification of liver mitochondrial DNA is associated with histological severity of nonalcoholic fatty liver disease (2013) Gut., 62, pp. 1356-1363 
504 |a Caldwell, S.H., De Freitas, L.A., Park, S.H., Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis (2009) Hepatology., 49, pp. 1888-1895 
504 |a Koliaki, C., Szendroedi, J., Kaul, K., Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis (2015) Cell Metab., 21, pp. 739-746 
504 |a Sanyal, A.J., Campbell-Sargent, C., Mirshahi, F., Nonalcoholic steatohepatitis: Association of insulin resistance and mitochondrial abnormalities (2001) Gastroenterology., 120, pp. 1183-1192 
504 |a Song, B.J., Akbar, M., Abdelmegeed, M.A., Mitochondrial dysfunction and tissue injury by alcohol, high fat, nonalcoholic substances and pathological conditions through post-translational protein modifications (2014) Redox Biol., 3, pp. 109-123 
504 |a Zeybel, M., Hardy, T., Robinson, S.M., Differential DNA methylation of genes involved in fibrosis progression in nonalcoholic fatty liver disease and alcoholic liver disease (2015) Clin Epigenetics., 7, p. 25 
504 |a Wyatt, G.R., Cohen, S.S., A new pyrimidine base from bacteriophage nucleic acids (1952) Nature., 170, pp. 1072-1073 
504 |a Laird, A., Thomson, J.P., Harrison, D.J., 5-Hydroxymethylcytosine profiling as an indicator of cellular state (2013) Epigenomics., 5, pp. 655-669 
504 |a Nestor, C.E., Ottaviano, R., Reddington, J., Tissue type is a major modifier of the 5-hydroxymethylcytosine content of human genes (2012) Genome Res., 22, pp. 467-477 
504 |a Thomson, J.P., Hunter, J.M., Lempiainen, H., Dynamic changes in 5-hydroxymethylation signatures underpin early and late events in drug exposed liver (2013) Nucleic Acids Res., 41, pp. 5639-5654 
504 |a Shock, L.S., Thakkar, P.V., Peterson, E.J., DNA methyltransferase 1, cytosine methylation, and cytosine hydroxymethylation in mammalian mitochondria (2011) Proc Natl Acad Sci USA., 108, pp. 3630-3635 
504 |a Bellizzi, D., D'Aquila, P., Scafone, T., The control region of mitochondrial DNA shows an unusual CpG and non-CpG methylation pattern (2013) DNA Res., 20, pp. 537-547 
504 |a Tahiliani, M., Koh, K.P., Shen, Y., Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1 (2009) Science., 324, pp. 930-935 
504 |a Xin, Y.J., Yuan, B., Yu, B., Tet1-mediated DNA demethylation regulates neuronal cell death induced by oxidative stress (2015) Sci Rep., 5, p. 7645 
504 |a Eguchi, A., Wree, A., Feldstein, A.E., Biomarkers of liver cell death (2014) J Hepatol., 60, pp. 1063-1074 
504 |a Kleiner, D.E., Brunt, E.M., Van, N.M., Design and validation of a histological scoring system for nonalcoholic fatty liver disease (2005) Hepatology., 41, pp. 1313-1321 
504 |a Brunt, E.M., Kleiner, D.E., Wilson, L.A., Nonalcoholic fatty liver disease (NAFLD) activity score and the histopathologic diagnosis in NAFLD: Distinct clinicopathologic meanings (2011) Hepatology., 53, pp. 810-820 
504 |a Skol, A.D., Scott, L.J., Abecasis, G.R., Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies (2006) Nat Genet., 38, pp. 209-213 
504 |a Jin, C., Lu, Y., Jelinek, J., TET1 is a maintenance DNA demethylase that prevents methylation spreading in differentiated cells (2014) Nucleic Acids Res., 42, pp. 6956-6971 
504 |a Williams, K., Christensen, J., Pedersen, M.T., TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity (2011) Nature., 473, pp. 343-348 
504 |a Williams, K., Christensen, J., Helin, K., DNA methylation: TET proteins-guardians of CpG islands (2012) EMBO Rep, 13, pp. 28-35 
504 |a Udali, S., Guarini, P., Moruzzi, S., Global DNA methylation and hydroxymethylation differ in hepatocellular carcinoma and cholangiocarcinoma and relate to survival rate (2015) Hepatology., 62, pp. 496-504 
504 |a Leers, M.P., Kolgen, W., Bjorklund, V., Immunocytochemical detection and mapping of a cytokeratin 18 neo-epitope exposed during early apoptosis (1999) J Pathol., 187, pp. 567-572 
504 |a Ivanov, M., Kals, M., Kacevska, M., Ontogeny, distribution and potential roles of 5-hydroxymethylcytosine in human liver function (2013) Genome Biol., 14, p. R83 
520 3 |a The 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification whose role in the pathogenesis of metabolic-related complex diseases remains unexplored; 5-hmC appears to be prevalent in the mitochondrial genome. The Ten-Eleven-Translocation (TET) family of proteins is responsible for catalyzing the conversion of 5-methylcytosine to 5-hmC. We hypothesized that epigenetic editing by 5-hmC might be a novel mechanism through which nonalcoholic fatty liver disease (NAFLD)-associated molecular traits could be explained. Hence, we performed an observational study to explore global levels of 5-hmC in fresh liver samples of patients with NAFLD and controls (n=90) using an enzyme-linked-immunosorbent serologic assay and immunohistochemistry. We also screened for genetic variation in TET 1-3 loci by next generation sequencing to explore its contribution to the disease biology. The study was conducted in 2 stages (discovery and replication) and included 476 participants. We observed that the amount of 5-hmC in the liver of both NAFLD patients and controls was relatively low (up to 0.1%); a significant association was found with liver mitochondrial DNA copy number (R=0.50, P=0.000382) and PPARGC1A-mRNA levels (R=-0.57, P=0.04). We did not observe any significant difference in the 5-hmC nuclear immunostaining score between NAFLD patients and controls; nevertheless, we found that patients with NAFLD (0.4-0.5) had significantly lower nonnuclear-5-hmC staining compared with controls (1.8-0.8), means-standard deviation, P=0.028. The missense p.Ile1123Met variant (TET1-rs3998860) was significantly associated with serum levels of caspase-generated CK-18 fragment-cell death biomarker in the discovery and replication stage, and the disease severity (odds ratio: 1.47, 95% confidence interval: 1.10-1.97; P=0.005). The p.Ile1762- Val substitution (TET2-rs2454206) was associated with liver PPARGC1A-methylation and transcriptional levels, and Type 2 diabetes. Our results suggest that 5-hmC might be involved in the pathogenesis of NAFLD by regulating liver mitochondrial biogenesis and PPARGC1A expression. Genetic diversity at TET loci suggests an ''epigenetic'' regulation of programmed liver-cell death and a TETmediated fine-tuning of the liver PPARGC1A-transcriptional program. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.  |l eng 
593 |a Department of Molecular Genetics and Biology of Complex Diseases, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina 
593 |a Biomedical Genomics and Evolution Laboratory, Ecology, Genetics and Evolution Department, Faculty of Science, IEGEBA, University of Buenos Aires-National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina 
593 |a Department of Pathology, Hospital Diego Thompson San Martin, Buenos Aires, Argentina 
593 |a Liver Unit, Medicine and Surgery Department, Hospital Abel Zubizarreta, Ciudad Autónoma de Buenos Aires, Argentina 
593 |a Department of Clinical and Molecular Hepatology, Institute of Medical Research A Lanari-IDIM, University of Buenos Aires-National Scientific and Technical Research Council (CONICET), Ciudad Autónoma de Buenos Aires, Argentina 
690 1 0 |a 5 HYDROXYMETHYLCYTOSINE 
690 1 0 |a CYTOKERATIN 18 
690 1 0 |a MESSENGER RNA 
690 1 0 |a MITOCHONDRIAL DNA 
690 1 0 |a PEPTIDES AND PROTEINS 
690 1 0 |a PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA 
690 1 0 |a TEN ELEVEN TRANSLOCATION 1 PROTEIN 
690 1 0 |a TEN ELEVEN TRANSLOCATION 2 PROTEIN 
690 1 0 |a TEN ELEVEN TRANSLOCATION 3 PROTEIN 
690 1 0 |a UNCLASSIFIED DRUG 
690 1 0 |a 5-HYDROXYMETHYLCYTOSINE 
690 1 0 |a CYTOSINE 
690 1 0 |a DNA BINDING PROTEIN 
690 1 0 |a HEAT SHOCK PROTEIN 
690 1 0 |a ONCOPROTEIN 
690 1 0 |a PPARGC1A PROTEIN, HUMAN 
690 1 0 |a TET1 PROTEIN, HUMAN 
690 1 0 |a TRANSCRIPTION FACTOR 
690 1 0 |a ABDOMINAL OBESITY 
690 1 0 |a ADULT 
690 1 0 |a APOPTOSIS 
690 1 0 |a ARTICLE 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a DISEASE SEVERITY 
690 1 0 |a DNA METHYLATION 
690 1 0 |a DNA MODIFICATION 
690 1 0 |a EPIGENETICS 
690 1 0 |a FEMALE 
690 1 0 |a GENE DOSAGE 
690 1 0 |a GENE LOCUS 
690 1 0 |a GENETIC SUSCEPTIBILITY 
690 1 0 |a GENETIC VARIABILITY 
690 1 0 |a HISTOPATHOLOGY 
690 1 0 |a HUMAN 
690 1 0 |a HUMAN TISSUE 
690 1 0 |a HYPERTENSION 
690 1 0 |a HYPERTRIGLYCERIDEMIA 
690 1 0 |a IMMUNOHISTOCHEMISTRY 
690 1 0 |a INSULIN RESISTANCE 
690 1 0 |a LIVER BIOPSY 
690 1 0 |a LIVER FIBROSIS 
690 1 0 |a LIVER HISTOLOGY 
690 1 0 |a LIVER MITOCHONDRION 
690 1 0 |a MAJOR CLINICAL STUDY 
690 1 0 |a MALE 
690 1 0 |a MIDDLE AGED 
690 1 0 |a MITOCHONDRIAL GENOME 
690 1 0 |a NEXT GENERATION SEQUENCING 
690 1 0 |a NON INSULIN DEPENDENT DIABETES MELLITUS 
690 1 0 |a NONALCOHOLIC FATTY LIVER 
690 1 0 |a OBSERVATIONAL STUDY 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN EXPRESSION 
690 1 0 |a PROTEIN METHYLATION 
690 1 0 |a SINGLE NUCLEOTIDE POLYMORPHISM 
690 1 0 |a STEATOSIS 
690 1 0 |a ANALOGS AND DERIVATIVES 
690 1 0 |a GENETIC EPIGENESIS 
690 1 0 |a GENETIC PREDISPOSITION 
690 1 0 |a GENETICS 
690 1 0 |a LIVER 
690 1 0 |a METABOLISM 
690 1 0 |a NON-ALCOHOLIC FATTY LIVER DISEASE 
690 1 0 |a ORGANELLE BIOGENESIS 
690 1 0 |a PATHOLOGY 
690 1 0 |a ADULT 
690 1 0 |a CYTOSINE 
690 1 0 |a DNA METHYLATION 
690 1 0 |a DNA-BINDING PROTEINS 
690 1 0 |a EPIGENESIS, GENETIC 
690 1 0 |a FEMALE 
690 1 0 |a GENETIC PREDISPOSITION TO DISEASE 
690 1 0 |a HEAT-SHOCK PROTEINS 
690 1 0 |a HUMANS 
690 1 0 |a LIVER 
690 1 0 |a MALE 
690 1 0 |a MIDDLE AGED 
690 1 0 |a MITOCHONDRIA, LIVER 
690 1 0 |a NON-ALCOHOLIC FATTY LIVER DISEASE 
690 1 0 |a ORGANELLE BIOGENESIS 
690 1 0 |a PROTO-ONCOGENE PROTEINS 
690 1 0 |a TRANSCRIPTION FACTORS 
700 1 |a Scian, R. 
700 1 |a Gianotti, T.F. 
700 1 |a Dopazo, H. 
700 1 |a Rohr, C. 
700 1 |a Martino, J.S. 
700 1 |a Castaño, G.O. 
700 1 |a Sookoian, S. 
773 0 |d Lippincott Williams and Wilkins, 2015  |g v. 94  |k n. 36  |p Medicine  |x 00257974  |t Medicine (United States) 
856 4 1 |u https://www.scopus.com/inward/record.uri?eid=2-s2.0-84941686246&doi=10.1097%2fMD.0000000000001480&partnerID=40&md5=73282b02a90d6f5726b8edd1f50a5c84  |y Registro en Scopus 
856 4 0 |u https://doi.org/10.1097/MD.0000000000001480  |y DOI 
856 4 0 |u https://hdl.handle.net/20.500.12110/paper_00257974_v94_n36_p_Pirola  |y Handle 
856 4 0 |u https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00257974_v94_n36_p_Pirola  |y Registro en la Biblioteca Digital 
961 |a paper_00257974_v94_n36_p_Pirola  |b paper  |c PE 
962 |a info:eu-repo/semantics/article  |a info:ar-repo/semantics/artículo  |b info:eu-repo/semantics/publishedVersion 
999 |c 85829