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Leonardo Elia, Paolo Kunderfranco, Pierluigi Carullo, Marco Vacchiano, Floriana Maria Farina, Ignacio Fernando Hall, Stefano Mantero, Cristina Panico, Roberto Papait, Gianluigi Condorelli, Manuela Quintavalle
Adult vascular smooth muscle cells (VSMCs) possess the peculiar ability to de-differentiate in response to extracellular cues, such as vascular damage and inflammation. De-differentiated VSMCs are proliferative, migratory, and have decreased contractile capacity. VSMC dedifferentiation contributes not only to vascular repair, but also to cardiovascular pathologies, such as intimal hyperplasia/restenosis in coronary artery or peripheral vascular diseases and arterial aneurysm. We here demonstrate the role of ubiquitin-like, containing PHD and RING finger domains, 1 (UHRF1) as an epigenetic master regulator of VSMC plasticity...
March 20, 2018: Journal of Clinical Investigation
Magdalena Dryglewska, Bogdan Kolarz, Maria Majdan
Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease that results in uncontrolled immune system activation and overproduction of autoantibodies. The pathogenesis of the disease is complex and not fully understood, nevertheless, genetic and environmental factors play an important role. So far, about 30 genes have been identified to be involved in the SLE pathomechanism. However, not all genetically predisposed individuals develop the disease. This phenomenon can be associated with epigenetic changes that occur under the influence of environmental factors...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Chun-Xiao Lu, Xiao-Li Wu, Guang-Yuan Zhang, Xiao-Ting Gu, Xin Ma, Dong-Xu He
Cancer is one of the most important health problems today; therefore, many researchers are focusing on exploring the mechanisms underlying its development and treatment. The field of cancer epigenetics has flourished in recent decades, and studies have shown that different epigenetic events, such as DNA methylation, histone modification, and noncoding RNA regulation, work together to influence cancer development and progression. In this short review, we summarize the interactions between methylation and noncoding RNAs that affect cancer development...
March 19, 2018: European Journal of Cancer Prevention
Mahnaz Rezaei, Fatemeh Eskandari, Abbas Mohammadpour-Gharehbagh, Mahdiyeh Harati-Sadegh, Batool Teimoori, Saeedeh Salimi
PURPOSE: PE is a pregnancy-specific complication, which genetic and epigenetic factors play key roles in its pathogenesis. DNA methylation is a main epigenetic alteration with important roles in gene regulation. Micro RNAs (miRNAs) as another member of epigenetic machinery regulate the gene expression and involve in different biological pathways including apoptosis and placental development. Therefore, the present study performed to assess the association between miRNA-34a promoter methylation and PE susceptibility...
March 20, 2018: Clinical and Experimental Hypertension: CHE
Philippa Melamed, Yahav Yosefzon, Cfir David, Anna Tsukerman, Lilach Pnueli
Discovery of the ten-eleven translocation 1 (TET) methylcytosine dioxygenase family of enzymes, nearly 10 years ago, heralded a major breakthrough in understanding the epigenetic modifications of DNA. Initially described as catalyzing the oxidation of methyl cytosine (5mC) to hydroxymethyl cytosine (5hmC), it is now clear that these enzymes can also catalyze additional reactions leading to active DNA demethylation. The association of TET enzymes, as well as the 5hmC, with active regulatory regions of the genome has been studied extensively in embryonic stem cells, although these enzymes are expressed widely also in differentiated tissues...
2018: Frontiers in Cell and Developmental Biology
Jebi Sudan, Meenakshi Raina, Ravinder Singh
Plants have evolved various defense mechanisms including morphological adaptations, cellular pathways, specific signalling molecules and inherent immunity to endure various abiotic stresses during different growth stages. Most of the defense mechanisms are controlled by stress-responsive genes by transcribing and translating specific genes. However, certain modifications of DNA and chromatin along with small RNA-based mechanisms have also been reported to regulate the expression of stress-responsive genes and constitute another line of defense for plants in their struggle against stresses...
March 2018: 3 Biotech
Lu Gan, Yanan Yang, Qian Li, Yi Feng, Tianshu Liu, Weijian Guo
Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a catalytic component of PRC2, catalyzes tri-methylation of histone H3 at Lys 27 (H3K27me3) to regulate gene expression through epigenetic machinery. EZH2 also functions both as a transcriptional suppressor and a transcriptional co-activator, depending on H3K27me3 or not and on the different cellular contexts. Unsurprisingly, numerous studies have highlighted the role of EZH2 in cancer development and progression. Through modulating critical gene expression, EZH2 promotes cell survival, proliferation, epithelial to mesenchymal, invasion, and drug resistance of cancer cells...
2018: Biomarker Research
Jiehua Zhou, Daniel Lazar, Haitang Li, Xin Xia, Sangeetha Satheesan, Paige Charlins, Denis O'Mealy, Ramesh Akkina, Sheena Saayman, Marc S Weinberg, John J Rossi, Kevin V Morris
Gene-based therapies represent a promising therapeutic paradigm for the treatment of HIV-1, as they have the potential to maintain sustained viral inhibition with reduced treatment interventions. Such an option may represent a long-term treatment alternative to highly active antiretroviral therapy. Methods: We previously described a therapeutic approach, referred to as transcriptional gene silencing (TGS), whereby small noncoding RNAs directly inhibit the transcriptional activity of HIV-1 by targeting sites within the viral promoter, specifically the 5' long terminal repeat (LTR)...
2018: Theranostics
Huihui Mao, Kai Wang, Yuehua Feng, Jun Zhang, Lili Pan, Yuxia Zhan, Haijun Sheng, Guanghua Luo
Background: The aberrant expression of long non-coding RNA (lncRNA) X inactivate-specific transcript (XIST) has been demonstrated to be involved in the tumourigenesis and the development of various cancers. Therefore, we conducted a meta-analysis to assess the prognostic role of lncRNA XIST expression in solid tumors. Methods: The databases of PubMed, EMBase, Web of Science, Cochrane library (up to Dec 31, 2017) were searched for the related studies and identified 15 eligible studies containing 1209 patients to include in the meta-analysis...
2018: Cancer Cell International
R C Laker, C Garde, D M Camera, W J Smiles, J R Zierath, J A Hawley, R Barrès
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
March 19, 2018: Scientific Reports
Raffaella Nativio, Greg Donahue, Amit Berson, Yemin Lan, Alexandre Amlie-Wolf, Ferit Tuzer, Jon B Toledo, Sager J Gosai, Brian D Gregory, Claudio Torres, John Q Trojanowski, Li-San Wang, F Brad Johnson, Nancy M Bonini, Shelley L Berger
In the version of this article initially published online, the fifth author's name was given as Alexander Amlie-Wolf. The correct name is Alexandre Amlie-Wolf. The error has been corrected in the print, PDF and HTML versions of this article.
March 19, 2018: Nature Neuroscience
Andrew D Kelly, Jozef Madzo, Priyanka Madireddi, Patricia Kropf, Charly R Good, Jaroslav Jelinek, Jean-Pierre J Issa
Acute myeloid leukemia (AML) often harbors mutations in epigenetic regulators, and also has frequent DNA hypermethylation, including the presence of CpG island methylator phenotypes (CIMPs). Although global hypomethylation is well known in cancer, the question of whether distinct demethylator phenotypes (DMPs) exist remains unanswered. Using Illumina 450k arrays for 194 patients from The Cancer Genome Atlas, we identified two distinct DMPs by hierarchical clustering: DMP.1 and DMP.2. DMP.1 cases harbored mutations in NPM1 (94%), FLT3 (71%) and DNMT3A (61%)...
March 7, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Daichi Inoue, Takeshi Fujino, Paul Sheridan, Yao-Zhong Zhang, Reina Nagase, Sayuri Horikawa, Zaomin Li, Hirotaka Matsui, Akinori Kanai, Makoto Saika, Rui Yamaguchi, Hiroko Kozuka-Hata, Kimihito Cojin Kawabata, Akihiko Yokoyama, Susumu Goyama, Toshiya Inaba, Seiya Imoto, Satoru Miyano, Mingjiang Xu, Feng-Chun Yang, Masaaki Oyama, Toshio Kitamura
ASXL1 plays key roles in epigenetic regulation of gene expression through methylation of histone H3K27, and disruption of ASXL1 drives myeloid malignancies, at least in part, via derepression of posterior HOXA loci. However, little is known about the identity of proteins that interact with ASXL1 and about the functions of ASXL1 in modulation of the active histone mark, such as H3K4 methylation. In this study, we demonstrate that ASXL1 is a part of a protein complex containing HCFC1 and OGT; OGT directly stabilizes ASXL1 by O-GlcNAcylation...
March 3, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Tao Wang, Zhong-Yi Qin, Liang-Zhi Wen, Yan Guo, Qin Liu, Zeng-Jie Lei, Wei Pan, Kai-Jun Liu, Xing-Wei Wang, Shu-Jie Lai, Wen-Jing Sun, Yan-Ling Wei, Lei Liu, Ling Guo, Yu-Qin Chen, Jun Wang, Hua-Liang Xiao, Xiu-Wu Bian, Dong-Feng Chen, Bin Wang
The evolutionarily conserved Hippo signaling pathway is a key regulator of stem cell self-renewal, differentiation, and organ size. While alterations in Hippo signaling are causally linked to uncontrolled cell growth and a broad range of malignancies, genetic mutations in the Hippo pathway are uncommon and it is unclear how the tumor suppressor function of the Hippo pathway is disrupted in human cancers. Here, we report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma (HCC)...
March 19, 2018: Cell Death and Differentiation
Hiroki Hamamoto, Kentaro Maemura, Kentaro Matsuo, Kohei Taniguchi, Yoshihisa Tanaka, Sugiko Futaki, Atsushi Takeshita, Akira Asai, Michihiro Hayashi, Yoshinobu Hirose, Yoichi Kondo, Kazuhisa Uchiyama
Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis. We previously showed that expression of Delta-like 3 (DLL3), a member of the family of Delta/Serrate/Lag2 ligands for the Notch receptor, is silenced by aberrant DNA methylation and that overexpression of DLL3 in an HCC cell line induces cellular apoptosis. However, how DLL3 expression is regulated during hepatocarcinogenesis is still unclear. Here, we show that silencing of DLL3 during hepatocarcinogenesis is closely related to viral infection, especially hepatitis B virus (HBV) infection (p = 0...
March 19, 2018: Scientific Reports
Yingying Zhang, Xulei Zheng, Hao Tan, Yilu Lu, Dachang Tao, Yunqiang Liu, Yongxin Ma
HDAC3 is involved in deacetylation of histone and non-histone proteins, having a key role in the regulation of gene transcription and also in the process of tumorgenesis. However, how HDAC3 is regulated in cancer remains largely unclear. Here, we showed that PIWIL2 can interact with HDAC3, leading to stabilization of HDAC3 from ubiquitin-mediated degradation by competitive association with E3 ubiquitin ligase Siah2. Furthermore, we found that expression of PIWIL2 enhanced HDAC3 activity via CK2α. PIWIL2 facilitated the interaction between HDAC3 and CK2α, thus exhibiting a promotion on the HDAC3 phosphorylation by CK2α...
March 19, 2018: Cell Death & Disease
Daniel L McCartney, Rosie M Walker, Stewart W Morris, Susan M Anderson, Barbara J Duff, Riccardo E Marioni, J Kirsty Millar, Shane E McCarthy, Niamh M Ryan, Stephen M Lawrie, Andrew R Watson, Douglas H R Blackwood, Pippa A Thomson, Andrew M McIntosh, W Richard McCombie, David J Porteous, Kathryn L Evans
Recent work has highlighted a possible role for altered epigenetic modifications, including differential DNA methylation, in susceptibility to psychiatric illness. Here, we investigate blood-based DNA methylation in a large family where a balanced translocation between chromosomes 1 and 11 shows genome-wide significant linkage to psychiatric illness. Genome-wide DNA methylation was profiled in whole-blood-derived DNA from 41 individuals using the Infinium HumanMethylation450 BeadChip (Illumina Inc., San Diego, CA)...
March 19, 2018: NPJ Schizophrenia
Dai Hatakeyama, Masaki Shoji, Seiya Yamayoshi, Rina Yoh, Naho Ohmi, Shiori Takenaka, Ayaka Saitoh, Yumie Arakaki, Aki Masuda, Tsugunori Komatsu, Rina Nagano, Masahiro Nakano, Takeshi Noda, Yoshihiro Kawaoka, Takashi Kuzuhara
Histone acetylation plays crucial roles in transcriptional regulation and chromatin organization. Viral RNA of the influenza virus interacts with its nucleoprotein (NP), whose function corresponds to that of eukaryotic histones. NP regulates viral replication and has been shown to undergo acetylation by the CREB-binding protein (CBP) from the host. However, whether NP is the target of other host acetyltransferases is unknown. Here, we show that influenza virus NP undergoes acetylation by the two host acetyltransferases GCN5 and P300/CBP-associated factor (PCAF) and that this modification affects viral polymerase activities...
March 19, 2018: Journal of Biological Chemistry
Michael M Mendelson
No abstract text is available yet for this article.
March 2018: Circ Genom Precis Med
Nicholas S Roetker, James S Pankow, Jan Bressler, Alanna C Morrison, Eric Boerwinkle
BACKGROUND: DNA methylation-based patterns of biological aging, known as epigenetic age acceleration, are predictive of all-cause mortality, but little is known about their association with cardiovascular disease (CVD). METHODS: We estimated 2 versions of epigenetic age acceleration (Horvath and Hannum) using whole-blood samples from 2543 blacks. Linear and Cox proportional hazards regression, respectively, were used to assess the association of age acceleration with carotid intima-media thickness (cross-sectionally) and incident cardiovascular events, including CVD mortality, myocardial infarction, fatal coronary heart disease, peripheral arterial disease, and heart failure, during a median 21-year follow-up...
March 2018: Circ Genom Precis Med
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