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Epigenetic silencing

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https://www.readbyqxmd.com/read/28934472/controlled-re-activation-of-epigenetically-silenced-tet-promoter-driven-transgene-expression-by-targeted-demethylation
#1
Natascha Gödecke, Lisha Zha, Shawal Spencer, Sara Behme, Pamela Riemer, Michael Rehli, Hansjörg Hauser, Dagmar Wirth
Faithful expression of transgenes in cell cultures and mice is often challenged by locus dependent epigenetic silencing. We investigated silencing of Tet-controlled expression cassettes within the mouse ROSA26 locus. We observed pronounced DNA methylation of the Tet promoter concomitant with loss of expression in mES cells as well as in differentiated cells and transgenic animals. Strikingly, the ROSA26 promoter remains active and methylation free indicating that this silencing mechanism specifically affects the transgene, but does not spread to the host's chromosomal neighborhood...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28933484/long-non-coding-rna-snhg17-is-an-unfavourable-prognostic-factor-and-promotes-cell-proliferation-by-epigenetically-silencing-p57-in-colorectal-cancer
#2
Zhonghua Ma, Shengying Gu, Min Song, Changsheng Yan, Bingqing Hui, Hao Ji, Jirong Wang, Jianping Zhang, Keming Wang, Qinghong Zhao
Recently, substantial evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in multiple cancers including colorectal cancer (CRC). Utilizing publicly available lncRNA-expression-profiling data from the Gene Expression Omnibus (GEO) dataset GSE21510, we screened SNHG17 as a new candidate lncRNA associated with CRC development and progression. We further demonstrated that SNHG17 was upregulated in CRC tissues, and that its overexpression was significantly correlated with tumor size, TNM stage, and lymph node metastasis in CRC patients...
September 21, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28931650/epigenetic-inactivation-of-tumour-suppressor-coding-and-non-coding-genes-in-human-cancer-an-update
#3
REVIEW
Pere Llinàs-Arias, Manel Esteller
Cancer cells undergo many different alterations during their transformation, including genetic and epigenetic events. The controlled division of healthy cells can be impaired through the downregulation of tumour suppressor genes. Here, we provide an update of the mechanisms in which epigenetically altered coding and non-coding tumour suppressor genes are implicated. We will highlight the importance of epigenetics in the different molecular pathways that lead to enhanced and unlimited capacity of division, genomic instability, metabolic shift, acquisition of mesenchymal features that lead to metastasis, and tumour plasticity...
September 2017: Open Biology
https://www.readbyqxmd.com/read/28928854/b-cell-translocation-gene-1-is-downregulated-by-promoter-methylation-in-ovarian-carcinoma
#4
Ji-Ye Kim, Sung-Im Do, Go Eun Bae, Hyun-Soo Kim
A better understanding of tumor biology is important in the identification of molecules that are downregulated in malignancy and in determining their role in tumor suppression. B-cell translocation gene 1 (BTG1) has been shown to act as a tumor suppressor in several types of human malignancy. In this study, we analyzed BTG1 expression in ovarian carcinoma cell lines, and we investigated the mechanism underlying the observed alterations. The methylation status of the BTG1 promoter region was determined by methylation-specific polymerase chain reaction, and the effect of demethylation on BTG1 expression was analyzed...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28927787/a-mimetic-of-the-msin3-binding-helix-of-nrsf-rest-ameliorates-abnormal-pain-behavior-in-chronic-pain-models
#5
Hiroshi Ueda, Jun-Ichi Kurita, Hiroyuki Neyama, Yuuka Hirao, Hiroyuki Kouji, Tadashi Mishina, Masaji Kasai, Hirofumi Nakano, Atsushi Yoshimori, Yoshifumi Nishimura
The neuron-restrictive silencing factor NRSF/REST binds to neuron-restrictive silencing elements in neuronal genes and recruits corepressors such as mSin3 to inhibit epigenetically neuronal gene expression. Because dysregulation of NRSF/REST is related to neuropathic pain, here, we have designed compounds to target neuropathic pain based on the mSin3-binding helix structure of NRSF/REST and examined their ability to bind to mSin3 by NMR. One compound, mS-11, binds strongly to mSin3 with a binding mode similar to that of NRSF/REST...
September 7, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28927055/silencing-dna-methyltransferase-1-leads-to-the-activation-of-the-esophageal-suppressor-gene-p16-in-vitro-and-in-vivo
#6
Jian Bai, Xue Zhang, Bangqing Liu, Haiyong Wang, Zhenzong Du, Jianfei Song
Previous studies have demonstrated that DNA methyltransferase 1 (DNMT1) is required for the maintenance of DNA methylation and epigenetic changes that may lead to the development of esophageal squamous cell carcinoma (ESCC). In order to investigate whether the silencing of DNMT1 protects tumor suppressor genes, including p16, and is able to be used as a potential therapy for human ESCC, short hairpin RNA targeting DNMT1 (shRNA-DNMT1) was synthesized and transfected into the human ESCC lines KYSE150 and KYSE410, which were then injected into the backs of nude mice prior to harvesting...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926746/effect-of-modeled-microgravity-on-uv-c-induced-interplant-communication-of-arabidopsis-thaliana
#7
Ting Wang, Wei Xu, Huasheng Li, Chenguang Deng, Hui Zhao, Yuejin Wu, Min Liu, Lijun Wu, Jinying Lu, Po Bian
Controlled ecological life support systems (CELSS) will be an important feature of long-duration space missions of which higher plants are one of the indispensable components. Because of its pivotal role in enabling plants to cope with environmental stress, interplant communication might have important implications for the ecological stability of such CELSS. However, the manifestations of interplant communication in microgravity conditions have yet to be fully elucidated. To address this, a well-established Arabidopsis thaliana co-culture experimental system, in which UV-C-induced airborne interplant communication is evaluated by the alleviation of transcriptional gene silencing (TGS) in bystander plants, was placed in microgravity modeled by a two-dimensional rotating clinostat...
September 6, 2017: Mutation Research
https://www.readbyqxmd.com/read/28923203/epigenetic-silencing-of-mirna-34a-in-human-cholangiocarcinoma-via-ezh2-and-dna-methylation-impact-on-regulation-of-notch-pathway
#8
Hyunjoo Kwon, Kyoungsub Song, Chang Han, Jinqiang Zhang, Lu Lu, Weina Chen, Tong Wu
Aberrant expression and regulation of miRNAs have been implicated in multiple stages of tumorigenic processes. The current study was designed to explore the biological function and epigenetic regulation of miR-34a in human cholangiocarcinoma (CCA). Our data show that the expression of miR-34a is decreased significantly in CCA cells compared with non-neoplastic biliary epithelial cells. Forced overexpression of miR-34a in CCA cells inhibited their proliferation and clonogenic capacity in vitro, and suppressed tumor xenograft growth in severe combined immunodeficiency mice...
October 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28918030/lncrna-trerna1-function-as-an-enhancer-of-snai1-promotes-gastric-cancer-metastasis-by-regulating-epithelial-mesenchymal-transition
#9
Huazhang Wu, Ying Hu, Xiufang Liu, Wei Song, Pihai Gong, Kun Zhang, Zhenxing Chen, Menghan Zhou, Xiaohui Shen, Yanyan Qian, Hong Fan
Long noncoding RNA (lncRNA) has been implicated in cancer, but little is known about the role of lncRNAs as regulators of tumor metastasis. In the present study, we demonstrate that lncRNA TRERNA1 acts like an enhancer of SNAI1 to promote cell invasion and migration and to contribute to metastasis of gastric cancer (GC). TRERNA1 is significantly unregulated in GCs and GC cell lines. Increased TRERNA1 is positively correlated with lymph node metastasis of GCs. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays revealed that TRERNA1 functions as a scaffold to recruit EZH2 to epigenetically silence epithelial-mesenchymal transition marker CDH1 by H3K27me3 of its promoter region...
September 15, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28916764/rapid-and-reversible-epigenome-editing-by-endogenous-chromatin-regulators
#10
Simon M G Braun, Jacob G Kirkland, Emma J Chory, Dylan Husmann, Joseph P Calarco, Gerald R Crabtree
Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28912274/structure-mechanism-and-regulation-of-polycomb-repressive-complex-2
#11
Lindsay E Moritz, Raymond C Trievel
Polycomb Repressive Complex 2 (PRC2) methylates lysine 27 in histone H3, a modification associated with epigenetic gene silencing. This complex plays a fundamental role in regulating cellular differentiation and development, and PRC2 overexpression and mutations have been implicated in numerous cancers. In this review, we examine recent studies elucidating the first crystal structures of the PRC2 core complex, yielding seminal insights into its catalytic mechanism, substrate specificity, allosteric regulation, and inhibition by a class of small molecules that are currently undergoing cancer clinical trials...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28903346/glutathione-peroxidase-7-suppresses-cancer-cell-growth-and-is-hypermethylated-in-gastric-cancer
#12
Zheng Chen, Tianling Hu, Shoumin Zhu, Kenichi Mukaisho, Wael El-Rifai, Dun-Fa Peng
Gastric cancer (GC) is one of the most common cancers in the world, and remains the third leading cause of cancer-related deaths worldwide. Glutathione peroxidase 7 (GPX7) is a member of GPX family which is downregulated in some cancer types. In this study, we investigated the expression, regulation, and molecular function of GPX7 in gastric cancer using 2D and 3D in vitro models and de-identified human tissue samples. Quantitative real-time RT-PCR, immunofluorescence, Western blot, 3D organotypic cultures, and pyrosequencing assays were used...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28900494/lhx6-an-independent-prognostic-factor-inhibits-lung-adenocarcinoma-progression-through-transcriptional-silencing-of-%C3%AE-catenin
#13
Juntang Yang, Fei Han, Wenbin Liu, Mingqian Zhang, Yongsheng Huang, Xianglin Hao, Xiao Jiang, Li Yin, Hongqiang Chen, Jia Cao, Huidong Zhang, Jinyi Liu
Introduction: Our previous study identified LIM homeobox domain 6 (LHX6) as a frequently epigenetically silenced tumor-suppressor gene in lung cancer. However, its clinical value has never been evaluated, and the in-depth anti-tumor mechanism remains unclear. Methods: Public database was used for lung cancer, lung adenocarcinoma and lung squamous carcinoma patients and tissue microarray data was used for lung adenocarcinoma patients to study prognostic outcome of LHX6 expression by Kaplan-Meier and Cox-regression analysis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28900001/samd7-is-a-cell-type-specific-prc1-component-essential-for-establishing-retinal-rod-photoreceptor-identity
#14
Yoshihiro Omori, Shun Kubo, Tetsuo Kon, Mayu Furuhashi, Hirotaka Narita, Taro Kominami, Akiko Ueno, Ryotaro Tsutsumi, Taro Chaya, Haruka Yamamoto, Isao Suetake, Shinji Ueno, Haruhiko Koseki, Atsushi Nakagawa, Takahisa Furukawa
Precise transcriptional regulation controlled by a transcription factor network is known to be crucial for establishing correct neuronal cell identities and functions in the CNS. In the retina, the expression of various cone and rod photoreceptor cell genes is regulated by multiple transcription factors; however, the role of epigenetic regulation in photoreceptor cell gene expression has been poorly understood. Here, we found that Samd7, a rod-enriched sterile alpha domain (SAM) domain protein, is essential for silencing nonrod gene expression through H3K27me3 regulation in rod photoreceptor cells...
September 12, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28898697/chronic-cigarette-smoke-induced-epigenomic-changes-precede-sensitization-of-bronchial-epithelial-cells-to-single-step-transformation-by-kras-mutations
#15
Michelle Vaz, Stephen Y Hwang, Ioannis Kagiampakis, Jillian Phallen, Ashwini Patil, Heather M O'Hagan, Lauren Murphy, Cynthia A Zahnow, Edward Gabrielson, Victor E Velculescu, Hariharan P Easwaran, Stephen B Baylin
We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells for transformation by a single oncogene. The smoke-induced chromatin changes include initial repressive polycomb marking of genes, later manifesting abnormal DNA methylation by 10 months. At this time, cells exhibit epithelial-to-mesenchymal changes, anchorage-independent growth, and upregulated RAS/MAPK signaling with silencing of hypermethylated genes, which normally inhibit these pathways and are associated with smoking-related non-small cell lung cancer...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28893347/mir-203-suppresses-bladder-cancer-cell-growth-and-targets-the-twist1
#16
Jie Shen, Jianhua Zhang, Minhui Xiao, Junfeng Yang, Ningnan Zhang
MiR-203 is an epigenetically silenced tumor-suppressive microRNA in tumors. This study was designed to investigate theeffects of miR-203 on the proliferation, migration, invasion and apoptosis of bladder cancer (BCa) cells. The expression levels of miR-203 in BCa tissues, the normal adjacent tissues, and the BCa cell lines were detected. BCa cells were transfected with miR-203 mimic and inhibitor to investigate the effect of miR-203 on cell functions and the epithelial mesenchymal transition (EMT). Cotransfection with miR-203 inhibitor and shRNA of the predicted target gene Twist1 (si-Twist1) was performed to investigate the target relationship of miR-203 and Twist1...
September 6, 2017: Oncology Research
https://www.readbyqxmd.com/read/28888056/comparison-of-genome-wide-analysis-techniques-to-dna-methylation-analysis-in-human-cancer
#17
REVIEW
Narges Soozangar, Mohammad Reza Sadeghi, Farhad Jeddi, Mohammad Hossein Somi, Masoud Shirmohamadi, Nasser Samadi
DNA methylation was the first epigenetic modification to be detected in human cancers with specific relation to aberrant gene expression. Herein, DNA methylation analysis explains how epigenetic patterns affect gene expression level. Hypermethylation at tumor suppressor gene loci leads to increased tumorigenesis due to tumor suppressor gene silencing, whereas global hypomethylation of CpG islands (CGIs) is followed by genomic instability and aberrant activation of multiple oncogenes. Therefore, characterization of the genes which silenced or activated epigenetically in human tumor cells can improve our understanding of cancer biology...
September 9, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28887438/-silencing-of-retrotransposons-by-setdb1-inhibits-the-interferon-response-in-acute-myeloid-leukemia
#18
Trinna L Cuellar, Anna-Maria Herzner, Xiaotian Zhang, Yogesh Goyal, Colin Watanabe, Brad A Friedman, Vasantharajan Janakiraman, Steffen Durinck, Jeremy Stinson, David Arnott, Tommy K Cheung, Subhra Chaudhuri, Zora Modrusan, Jonas Martin Doerr, Marie Classon, Benjamin Haley
A propensity for rewiring genetic and epigenetic regulatory networks, thus enabling sustained cell proliferation, suppression of apoptosis, and the ability to evade the immune system, is vital to cancer cell propagation. An increased understanding of how this is achieved is critical for identifying or improving therapeutic interventions. In this study, using acute myeloid leukemia (AML) human cell lines and a custom CRISPR/Cas9 screening platform, we identify the H3K9 methyltransferase SETDB1 as a novel, negative regulator of innate immunity...
September 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28885261/epigenetic-alterations-in-bone-and-soft-tissue-tumors
#19
John Wojcik, Kumarasen Cooper
Human malignancies are driven by heritable alterations that lead to unchecked cellular proliferation, invasive growth and distant spread. Heritable changes can arise from changes in DNA sequence, or, alternatively, through altered gene expression rooted in epigenetic mechanisms. In recent years, high-throughput sequencing of tumor genomes has revealed a central role for mutations in epigenetic regulatory complexes in oncogenic processes. Through interactions with or direct modifications of chromatin, these proteins help control the accessibility of genes, and thus the transcriptional profile of a cell...
September 6, 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28884294/a-concise-review-of-microrna-exploring-the-insights-of-microrna-regulations-in-bacterial-viral-and-metabolic-diseases
#20
REVIEW
Ahsan Naveed, Sajjad Ur-Rahman, Sabahat Abdullah, Muhammad Ammar Naveed
MicroRNA (miRNA) is a small section of ribonucleic acid (RNA) that reduces the protein formation by making the pair of the complementary piece of mRNA. The genes of miRNA are present as transcriptional or polycistronic units in the chromosomes. The cellular multiplication, separation and existence like the multitude of genetic functions are affected by miRNA. Nearly 50% of identified miRNA are located in the residence in the intronic part of the genes. The mature miRNA is yielded in two steps. Drosha and RNA-induced silencing complex are the catalysts that play an important role in miRNA synthesis...
September 7, 2017: Molecular Biotechnology
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