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Epigenetic modification

J Feng, X Y Gong, Y J Jia, K Q Liu, Y Li, X B Dong, Q Y Fang, K Ru, Q H Li, H J Wang, X L Zhao, Y N Jia, Y Song, Z Tian, M Wang, K J Tang, J X Wang, Y C Mi
Objective: To investigate the spectrum of gene mutations in adult patients with B-acute lymphoblastic leukemia (B-ALL), and to analyze the influences of different gene mutations on prognosis. Methods: DNA samples from 113 adult B-ALL patients who administered from June 2009 to September 2015 were collected. Target-specific next generation sequencing (NGS) approach was used to analyze the mutations of 112 genes (focused on the specific mutational hotspots) and all putative mutations were compared against multiple databases to calculate the frequency spectrum...
February 14, 2018: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Zengrong Zhang, Huarui Du, Lijun Bai, Chaowu Yang, Qingyun Li, Xiaocheng Li, Mohan Qiu, Chunlin Yu, Zongrong Jiang, Xiaoyu Jiang, Lan Liu, Chenming Hu, Bo Xia, Xia Xiong, Xiaoyan Song, Xiaosong Jiang
BACKGROUND: Tibetan chickens living at high altitudes show specific adaptations to high-altitude conditions, but the epigenetic modifications associated with these adaptations have not been characterized. RESULTS: We investigated the genome-wide DNA methylation patterns in Tibetan chicken blood by using whole genome bisulfite sequencing. Generally, Tibetan chickens exhibited analogous methylation patterns to that of lowland chickens. A total of 3.92% of genomic cytosines were methylcytosines and 51...
2018: PloS One
Hirofumi Noguchi, Chika Miyagi-Shiohira, Yoshiki Nakashima
Induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells. The pattern of expressed genes, DNA methylation, and covalent histone modifications in iPS cells are very similar to those in ES cells. However, it has recently been shown that, following the reprogramming of mouse/human iPS cells, epigenetic memory is inherited from the parental cells. These findings suggest that the phenotype of iPS cells may be influenced by their cells of origin and that their skewed differentiation potential may prove useful in the generation of differentiated cell types that are currently difficult to produce from ES/iPS cells for the treatment of human diseases...
March 21, 2018: International Journal of Molecular Sciences
Sabine Wächter, Alexander I Damanakis, Moritz Elxnat, Silvia Roth, Annette Wunderlich, Frederik A Verburg, Sebastian A Fellinger, Detlef K Bartsch, Pietro Di Fazio
Epigenetic modifications have been identified as being responsible for the de-differentiation of thyroid tissue and its malignant transformation. Cell proliferation inhibitory effects of the pan-deacetylase inhibitors panobinostat, SAHA and Trichostatin A (TSA), the modulation of the sodium iodide symporter (NIS; SLC5A5), thyroid transcription factor 1 (TTF1), high mobility group A2 (HMGA2), and H19 and their putative targeting miRNAs have been evaluated in vitro. The cell viability was measured in five thyroid cancer cell lines (FTC133, TPC1, BCPAP, 8505C, C643) by real time cell analyzer xCELLigence...
March 21, 2018: Journal of Clinical Medicine
A-K Reinhold, E Jentho, S T Schäfer, M Bauer, H L Rittner
Epigenetics, i.e. an altered reading of the genome without altering the genes themselves is a growing scientific field. A distinction is made between changes in the DNA by modification of the histones and non-coding RNA that alter the messenger (m)RNAs. Epigenetic modifications can be triggered by personal circumstances or other external factors and therefore influence the occurrence of diseases. Epigenetics are therefore of particular interest to anesthesiologists, pain specialists and intensive care physicians, as anesthetic drugs may have a long-term influence on protein transcription leading for example to alterations in neurocognition after anesthesia, chronification of postoperative pain and immune response in sepsis...
March 20, 2018: Der Anaesthesist
Khaled Elmasry, Riyaz Mohamed, Isha Sharma, Nehal M Elsherbiny, Yutao Liu, Mohamed Al-Shabrawey, Amany Tawfik
To study Hyperhomocysteinemia (HHcy)-induced epigenetic modifications as potential mechanisms of blood retinal barrier (BRB) dysfunction, retinas isolated from three- week-old mice with elevated level of Homocysteine (Hcy) due to lack of the enzyme cystathionine β-synthase ( cbs-/- , cbs+/- and cbs+/+ ), human retinal endothelial cells (HRECs), and human retinal pigmented epithelial cells (ARPE-19) treated with or without Hcy were evaluated for (1) histone deacetylases (HDAC), (2) DNA methylation (DNMT), and (3) miRNA analysis...
February 27, 2018: Oncotarget
Yan Li, Wenwen Zhang, Pengying Liu, Yumei Xu, Lin Tang, Weiwei Chen, Xiaoxiang Guan
Introduction: FENDRR is a long non-coding RNA (lncRNA) that mediates the modification of the epigenetic landscape of target promoters by binding to polycomb repressive complex 2. However, the role of FENDRR in breast cancer remains unknown. Materials and methods: We detected the expression of FENDRR in 52 breast cancer patients' tissues and five breast cancer cell lines. The association between FENDRR expression and clinicopathological features and prognosis of breast cancer patients was also analyzed...
2018: OncoTargets and Therapy
Xiang Li, Erchang Shang, Qiang Dong, Yingfeng Li, Jing Zhang, Shaohua Xu, Zuodong Zhao, Wei Shao, Cong Lv, Yong Zheng, Hailin Wang, Xiaoguang Lei, Bing Zhu, Zhuqiang Zhang
Regulation of gene expression by epigenetic modifications such as DNA methylation is crucial for developmental and disease processes, including cell differentiation and cancer development. Genes repressed by DNA methylation can be derepressed by various compounds that target DNA methyltransferases, histone deacetylases, and other regulatory factors. However, some additional, unknown mechanisms that promote DNA methylation-mediated gene silencing may exist. Chemical agents that can counteract the effects of epigenetic repression that is not regulated by DNA methyltransferases or histone deacetylases therefore may be of research interest...
March 20, 2018: Journal of Biological Chemistry
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
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
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
Christina M Ferrer, Marielle Alders, Alex V Postma, Seonmi Park, Mark A Klein, Murat Cetinbas, Eva Pajkrt, Astrid Glas, Silvana van Koningsbruggen, Vincent M Christoffels, Marcel M A M Mannens, Lia Knegt, Jean-Pierre Etchegaray, Ruslan I Sadreyev, John M Denu, Gustavo Mostoslavsky, Merel C van Maarle, Raul Mostoslavsky
It has been well established that histone and DNA modifications are critical to maintaining the equilibrium between pluripotency and differentiation during early embryogenesis. Mutations in key regulators of DNA methylation have shown that the balance between gene regulation and function is critical during neural development in early years of life. However, there have been no identified cases linking epigenetic regulators to aberrant human development and fetal demise. Here, we demonstrate that a homozygous inactivating mutation in the histone deacetylase SIRT6 results in severe congenital anomalies and perinatal lethality in four affected fetuses...
March 19, 2018: Genes & Development
Alice Pasini, Oliver J Brand, Gisli Jenkins, Alan J Knox, Linhua Pang
Cyclooxygenase-2 (COX-2), with its main antifibrotic metabolite PGE2 , is regarded as an antifibrotic gene. Repressed COX-2 expression and deficient PGE2 have been shown to contribute to the activation of lung fibroblasts and excessive deposition of collagen in pulmonary fibrosis. We have previously demonstrated that COX-2 expression in lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF) is epigenetically silenced and can be restored by epigenetic inhibitors. This study aimed to investigate whether COX-2 downregulation induced by the profibrotic cytokine transforming growth factor-β1 (TGF-β1) in normal lung fibroblasts could be prevented by epigenetic inhibitors...
March 16, 2018: Biochimica et Biophysica Acta
Bing Li, Jie Zhao, Jian-Xiong Ma, Guo-Min Li, Yang Zhang, Guo-Sheng Xing, Jun Liu, Xin-Long Ma
Disuse osteoporosis (DOP) is a common complication of the lack of mechanical loading. The precise mechanism underlying DOP remains unknown, although epigenetic modifications may be a major cause. Recently, cumulative research has revealed that DNA methyltransferase (DNMT) proteins can catalyze the conversion of cytosine to 5-methylcytosine (5mC), altering the epigenetic state of DNA. Here, we report that DNMT1 expression and lncRNA-H19 methylation are upregulated in the femoral tissues of DOP rats, accompanied with inhibited Erk signaling pathway...
March 16, 2018: Bone
Rong Deng, Na Shen, Yang Yang, Hongliang Yu, Shuping Xu, Ying-Wei Yang, Shujun Liu, Kamel Meguellati, Fei Yan
Leukemia remains a fatal disease for most patients and novel therapeutic strategies are urgently needed. Aberrant DNA methylation is an epigenetic modification that is important in the initiation and progression of leukemia. Here, we demonstrated NCL/miR-221/NFκB/DNMT1 axis as a new molecular pathway promoting aggressive acute myeloid leukemia (AML) leukemogenesis and successfully designed and prepared a nuclear localization signal (NLS) peptide-targeted gold nanoparticles with co-loaded anti-221 and AS1411 (NPsN-AS1411/a221), which can specifically target NCL/miR-221/NFκB/DNMT1 signaling pathway in AML...
March 14, 2018: Biomaterials
John M Atack, Yuedong Yang, Kate L Seib, Yaoqi Zhou, Michael P Jennings
Many bacteria utilize simple DNA sequence repeats as a mechanism to randomly switch genes on and off. This process is called phase variation. Several phase-variable N6-adenine DNA-methyltransferases from Type III restriction-modification systems have been reported in bacterial pathogens. Random switching of DNA methyltransferases changes the global DNA methylation pattern, leading to changes in gene expression. These epigenetic regulatory systems are called phasevarions - phase-variable regulons. The extent of these phase-variable genes in the bacterial kingdom is unknown...
March 15, 2018: Nucleic Acids Research
Puneet, Hasan Raza Kazmi, Soni Kumari, Satendra Tiwari, A Khanna, Gopeshwar Narayan
Gastric cancer is one of the most common malignancy worldwide. The various genetic and epigenetic events have been found to be associated with its carcinogenesis. The epigenetic is a heritable and transient/reversible change in the gene expression that is not accompanied by modification in the DNA sequence. This event is characterized by the alteration in the promoter CpG island of the gene or histone modification. These events are associated with silencing of critical tumor suppressor gene and activation of oncogenes leading to carcinogenesis...
March 19, 2018: Pathology Oncology Research: POR
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