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Epigenetic silencing

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https://www.readbyqxmd.com/read/28811977/epigenetic-regulation-of-the-extrinsic-oncosuppressor-ptx3-gene-in-inflammation-and-cancer
#1
Marcello Rubino, Paolo Kunderfranco, Gianluca Basso, Carolina Magdalen Greco, Fabio Pasqualini, Simone Serio, Massimo Roncalli, Luigi Laghi, Alberto Mantovani, Roberto Papait, Cecilia Garlanda
PTX3 is a component of the humoral arm of innate immunity and an extrinsic oncosuppressor gene taming tumor-promoting inflammation. Here, we show that two enhancers differently regulate PTX3 expression: enhancer 1, located 230 kb upstream of PTX3 promoter, mediated the action of inflammatory transcription factors; and enhancer 2, encompassing PTX3 second exon, was implicated in pre-initiation complex assembly. Polycomb repressive complex 2 silenced these regulatory elements and the promoter in basal condition...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28808358/mbd2-regulates-th17-cell-differentiation-and-experimental-severe-asthma-by-affecting-irf4-expression
#2
Aijun Jia, Yueling Wang, Wenjin Sun, Bing Xiao, Yan Wei, Lulu Qiu, Lin Mu, Li Xu, Jianmin Li, Xiufeng Zhang, Da Liu, Cong Peng, Dongshan Zhang, Xudong Xiang
Th17 cells and IL-17 participate in airway neutrophil infiltration characteristics in the pathogenesis of severe asthma. Methyl-CpG binding domain protein 2 (MBD2) expression increased in CD4(+) T cells in peripheral blood samples of asthma patients. However, little is known about that epigenetic regulation of MBD2 in both immunological pathogenesis of experimental severe asthma and CD4(+) T cell differentiation. Here, we established a neutrophil-predominant severe asthma model, which was characterized by airway hyperresponsiveness (AHR), BALF neutrophil granulocyte (NEU) increase, higher NEU and IL-17 protein levels, and more Th17 cell differentiation...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28808009/a-protein-complex-regulates-rna-processing-of-intronic-heterochromatin-containing-genes-in-arabidopsis
#3
Cheng-Guo Duan, Xingang Wang, Lingrui Zhang, Xiansong Xiong, Zhengjing Zhang, Kai Tang, Li Pan, Chuan-Chih Hsu, Huawei Xu, W Andy Tao, Heng Zhang, Jian-Kang Zhu
In several eukaryotic organisms, heterochromatin (HC) in the introns of genes can regulate RNA processing, including polyadenylation, but the mechanism underlying this regulation is poorly understood. By promoting distal polyadenylation, the bromo-adjacent homology (BAH) domain-containing and RNA recognition motif-containing protein ASI1 and the H3K9me2-binding protein EDM2 are required for the expression of functional full-length transcripts of intronic HC-containing genes in Arabidopsis Here we report that ASI1 and EDM2 form a protein complex in vivo via a bridge protein, ASI1-Immunoprecipitated Protein 1 (AIPP1), which is another RNA recognition motif-containing protein...
August 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28806732/loss-of-the-chromatin-modifier-kdm2aa-causes-brafv600e-independent-spontaneous-melanoma-in-zebrafish
#4
Catherine M Scahill, Zsofia Digby, Ian M Sealy, Sonia Wojciechowska, Richard J White, John E Collins, Derek L Stemple, Till Bartke, Marie E Mathers, E Elizabeth Patton, Elisabeth M Busch-Nentwich
KDM2A is a histone demethylase associated with transcriptional silencing, however very little is known about its in vivo role in development and disease. Here we demonstrate that loss of the orthologue kdm2aa in zebrafish causes widespread transcriptional disruption and leads to spontaneous melanomas at a high frequency. Fish homozygous for two independent premature stop codon alleles show reduced growth and survival, a strong male sex bias, and homozygous females exhibit a progressive oogenesis defect. kdm2aa mutant fish also develop melanomas from early adulthood onwards which are independent from mutations in braf and other common oncogenes and tumour suppressors as revealed by deep whole exome sequencing...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28802234/paqr3-overexpression-suppresses-the-aggressive-phenotype-of-esophageal-squamous-cell-carcinoma-cells-via-inhibition-of-erk-signaling
#5
Ge Bai, Jianhu Chu, Mayinur Eli, Yongxing Bao, Hao Wen
Progestin and adipoQ receptor family member 3 (PAQR3) has exhibited anticancer activity in multiple malignancies. However, its expression and function in esophageal squamous cell carcinoma (ESCC) is still elusive. In this work, we examined the expression of PAQR3 in 40 surgically resected ESCC specimens and their adjacent normal tissues. The expression of PAQR3 in ESCC cell lines was measured after treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-Aza-CdR). The effects of overexpression of PAQR3 on cell proliferation, colony formation, invasion, and tumorigenesis were investigated...
August 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28801683/regulation-of-tumour-related-genes-by-dynamic-epigenetic-alteration-at-enhancer-regions-in-gastric-epithelial-cells-infected-by-epstein-barr-virus
#6
Atsushi Okabe, Sayaka Funata, Keisuke Matsusaka, Hiroe Namba, Masaki Fukuyo, Bahityar Rahmutulla, Motohiko Oshima, Atsushi Iwama, Masashi Fukayama, Atsushi Kaneda
Epstein-Barr virus (EBV) infection is associated with tumours such as Burkitt lymphoma, nasopharyngeal carcinoma, and gastric cancer. We previously showed that EBV(+) gastric cancer presents an extremely high-methylation epigenotype and this aberrant DNA methylation causes silencing of multiple tumour suppressor genes. However, the mechanisms that drive EBV infection-mediated tumorigenesis, including other epigenomic alteration, remain unclear. We analysed epigenetic alterations induced by EBV infection especially at enhancer regions, to elucidate their contribution to tumorigenesis...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801671/the-cpg-sites-of-the-cbx3-ubiquitous-chromatin-opening-element-are-critical-structural-determinants-for-the-anti-silencing-function
#7
Jessica Kunkiel, Natascha Gödecke, Mania Ackermann, Dirk Hoffmann, Axel Schambach, Nico Lachmann, Dagmar Wirth, Thomas Moritz
Suppression of therapeutic transgene expression from retroviral gene therapy vectors by epigenetic defence mechanisms represents a problem that is particularly encountered in pluripotent stem cells (PSCs) and their differentiated progeny. Transgene expression in these cells, however, can be stabilised by CpG-rich ubiquitous chromatin opening elements (UCOEs). In this context we recently demonstrated profound anti-silencing properties for the small (679 bp) CBX3-UCO element and we now confirmed this observation in the context of the defined murine chromosomal loci ROSA26 and TIGRE...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28797712/estrogen-receptor-beta-as-epigenetic-mediator-of-mir-10b-and-mir-145-in-mammary-cancer
#8
Zoi Piperigkou, Marco Franchi, Martin Götte, Nikos K Karamanos
Even though the role of estrogen receptor alpha (ERα) in the modulation of breast cancer cells' behavior is thoroughly studied, the biological functions of its isoform, ERβ, are less elucidated. The suppression of ERβ in the aggressive ERα-negative MDA-MB-231 breast cancer cells resulted in the inhibition of epithelial to mesenchymal transition (EMT) and major changes in the basic functional properties and expression levels of certain matrix components of breast cancer cells. This arrest in metastatic potential of breast cancer cells suggests the contribution of ERβ in the induction of a more aggressive phenotype in MDA-MB-231 breast cancer cells...
August 8, 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/28796262/long-noncoding-rna-crnde-promotes-colorectal-cancer-cell-proliferation-via-epigenetically-silencing-dusp5-cdkn1a-expression
#9
Jie Ding, Juan Li, HaiYan Wang, Yun Tian, Min Xie, XueZhi He, Hao Ji, Zhonghua Ma, Bingqing Hui, Keming Wang, Guozhong Ji
Evidence indicates that long non-coding RNAs (lncRNAs) play a critical role in the regulation of tumor cellular processes, such as proliferation, apoptosis, and metastasis. LncRNA CRNDE (Colorectal Neoplasia Differentially Expressed) is located at human chromosome 16 and has been found overexpressed in a variety of cancers including colorectal cancer (CRC). In this paper, we report that lncRNA CRNDE expression was remarkably upregulated in CRC tissues and that lncRNA CRNDE overexpression was positively correlated with advanced pathological stages and larger tumor sizes...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28794029/coordinate-regulation-of-tet2-and-ebna2-control-dna-methylation-state-of-latent-epstein-barr-virus
#10
Fang Lu, Andreas Wiedmer, Kayla A Martin, Priyankara J M S Wickramasinghe, Andrew V Kossenkov, Paul M Lieberman
Epstein-Barr Virus (EBV) latency and its associated carcinogenesis are regulated by dynamic changes in DNA methylation of both virus and host genomes. We show here that the Ten-Eleven Translocation 2 (TET2) gene, implicated in hydroxymethylation and active DNA demethylation, is a key regulator of EBV latency type DNA methylation patterning. EBV latency types are defined by DNA methylation patterns that restrict expression of viral latency genes. We show that TET2 mRNA and protein expression correlate with the highly demethylated EBV type III latency program permissive for expression of EBNA2, EBNA3s, and LMP transcripts...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28792704/epigenetic-modification-of-microrna-205-and-its-association-with-glioblastoma-multiform
#11
Asghar Ghasemi, Soudabeh Fallah
BACKGROUND: Deregulated expressions of tumor-suppressive microRNAs (miRNAs) by epigenetic aberrations has a critical role in tumorigenesis. The aim of the present study was to investigate the epigenetic aberrations of miR205 and to understand how this modification may contribute to molecular events in glioblastoma multiform (GBM). METHODS: Quantitative RT-PCR and bisulfite genomic sequencing techniques were used to investigate gene expression and methylation levels of miR-205 in GBM tissues (n = 23), their matched adjacent normal tissues (n = 23) and glioblastoma U87MG cell line...
July 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28790204/bacterial-chromatin-structural-proteins-regulate-the-bimodal-expression-of-the-locus-of-enterocyte-effacement-lee-pathogenicity-island-in-enteropathogenic-escherichia-coli
#12
Hervé Leh, Ahmad Khodr, Marie-Christine Bouger, Bianca Sclavi, Sylvie Rimsky, Stéphanie Bury-Moné
In enteropathogenic Escherichia coli (EPEC), the locus of enterocyte effacement (LEE) encodes a type 3 secretion system (T3SS) essential for pathogenesis. This pathogenicity island comprises five major operons (LEE1 to LEE5), with the LEE5 operon encoding T3SS effectors involved in the intimate adherence of bacteria to enterocytes. The first operon, LEE1, encodes Ler (LEE-encoded regulator), an H-NS (nucleoid structuring protein) paralog that alleviates the LEE H-NS silencing. We observed that the LEE5 and LEE1 promoters present a bimodal expression pattern, depending on environmental stimuli...
August 8, 2017: MBio
https://www.readbyqxmd.com/read/28783698/maintenance-of-macrophage-transcriptional-programs-and-intestinal-homeostasis-by-epigenetic-reader-sp140
#13
Stuti Mehta, D Alexander Cronkite, Megha Basavappa, Tahnee L Saunders, Fatemeh Adiliaghdam, Hajera Amatullah, Sara A Morrison, Jose D Pagan, Robert M Anthony, Pierre Tonnerre, Georg M Lauer, James C Lee, Sreehaas Digumarthi, Lorena Pantano, Shannan J Ho Sui, Fei Ji, Ruslan Sadreyev, Chan Zhou, Alan C Mullen, Vinod Kumar, Yang Li, Cisca Wijmenga, Ramnik J Xavier, Terry K Means, Kate L Jeffrey
Epigenetic "readers" that recognize defined posttranslational modifications on histones have become desirable therapeutic targets for cancer and inflammation. SP140 is one such bromodomain- and plant homeodomain (PHD)-containing reader with immune-restricted expression, and single-nucleotide polymorphisms (SNPs) within SP140 associate with Crohn's disease (CD). However, the function of SP140 and the consequences of disease-associated SP140 SNPs have remained unclear. We show that SP140 is critical for transcriptional programs that uphold the macrophage state...
March 3, 2017: Science Immunology
https://www.readbyqxmd.com/read/28783689/inhibition-of-hdac8-and-hdac9-by-microbial-short-chain-fatty-acids-breaks-immune-tolerance-of-the-epidermis-to-tlr-ligands
#14
James A Sanford, Ling-Juan Zhang, Michael R Williams, Jon A Gangoiti, Chun-Ming Huang, Richard L Gallo
Epidermal keratinocytes participate in immune defense through their capacity to recognize danger, trigger inflammation, and resist infection. However, normal skin immune function must tolerate contact with an abundant community of commensal microbes without inflammation. We hypothesized that microbial environmental conditions dictate the production of molecules that influence epigenetic events and cause keratinocytes to break innate immune tolerance. Propionibacterium acnes, a commensal skin bacterium, produced the short-chain fatty acids (SCFAs) propionate and valerate when provided a lipid source in hypoxic growth conditions, and these SCFAs inhibited histone deacetylase (HDAC) activity...
October 28, 2016: Science Immunology
https://www.readbyqxmd.com/read/28782042/polycomb-repressive-complex-1-modifies-transcription-of-active-genes
#15
Michelle Pherson, Ziva Misulovin, Maria Gause, Kathie Mihindukulasuriya, Amanda Swain, Dale Dorsett
This study examines the role of Polycomb repressive complex 1 (PRC1) at active genes. The PRC1 and PRC2 complexes are crucial for epigenetic silencing during development of an organism. They are recruited to Polycomb response elements (PREs) and establish silenced domains over several kilobases. Recent studies show that PRC1 is also directly recruited to active genes by the cohesin complex. Cohesin participates broadly in control of gene transcription, but it is unknown whether cohesin-recruited PRC1 also plays a role in transcriptional control of active genes...
August 2017: Science Advances
https://www.readbyqxmd.com/read/28781076/epigenetic-reprogramming-of-lineage-committed-human-mammary-epithelial-cells-requires-dnmt3a-and-loss-of-dot1l
#16
Jerrica L Breindel, Adam Skibinski, Maja Sedic, Ania Wronski-Campos, Wenhui Zhou, Patricia J Keller, Joslyn Mills, James Bradner, Tamer Onder, Charlotte Kuperwasser
Organogenesis and tissue development occur through sequential stepwise processes leading to increased lineage restriction and loss of pluripotency. An exception to this appears in the adult human breast, where rare variant epithelial cells exhibit pluripotency and multilineage differentiation potential when removed from the signals of their native microenvironment. This phenomenon provides a unique opportunity to study mechanisms that lead to cellular reprogramming and lineage plasticity in real time. Here, we show that primary human mammary epithelial cells (HMECs) lose expression of differentiated mammary epithelial markers in a manner dependent on paracrine factors and epigenetic regulation...
July 25, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28780440/epstein-barr-virus-a-master-epigenetic-manipulator
#17
REVIEW
Rona S Scott
Like all herpesviruses, the ability of Epstein-Barr virus (EBV) to establish life-long persistent infections is related to a biphasic viral lifecycle that involves latency and reactivation/lytic replication. Memory B cells serve as the EBV latency compartment where silencing of viral gene expression allows maintenance of the viral genome, avoidance of immune surveillance, and life-long carriage. Upon viral reactivation, viral gene expression is induced for replication, progeny virion production, and viral spread...
August 3, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28780076/bmi1-and-mel18-promote-colitis-associated-cancer-in-mice-via-reg3b-and-stat3
#18
Xicheng Liu, Wendi Wei, Xiaowei Li, Pengcheng Shen, Dapeng Ju, Zhen Wang, Rukui Zhang, Fu Yang, Chunyan Chen, Kun Cao, Guoli Zhu, Hongyan Chen, Liang Chen, Jianhua Sui, Erquan Zhang, Kaichun Wu, Fengchao Wang, Liping Zhao, Rongwen Xi
BACKGROUND & AIMS: Polycomb group proteins are epigenetic factors that silence gene expression; they are dysregulated in cancer cells and contribute to carcinogenesis by unclear mechanisms. We investigated whether BMI1 proto-oncogene, polycomb ring finger (BMI1) and polycomb group ring finger 2 (PCGF2, also called MEL18) are involved in initiation and progression of colitis-associated cancer (CAC) in mice. METHODS: We generated mice containing floxed alleles of Bmi1 and/or Mel18 and/or Reg3b using the villin-Cre promoter (called Bmi1(ΔIEC), Mel18(ΔIEC), DKO, and TKO mice)...
August 2, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28775176/epigenetic-silencing-of-lpp-mir-28-in-multiple-myeloma
#19
Zhenhai Li, Kwan Yeung Wong, Godfrey Chi-Fung Chan, Chor Sang Chim
AIMS: miR-28-5- is a tumour suppressor microRNA implicated in cancers. As a CpG island is absent in miR-28-5- but present in its host gene, LPP (LIM domain containing preferred translocation partner in lipoma), we hypothesized that miR-28-5p is epigenetically silenced by promoter DNA methylation of its host gene in multiple myeloma. METHODS: Methylation-specific PCR, verified by quantitative bisulfite pyrosequencing, was employed to study methylation of LPP/miR-28 in healthy controls (n=10), human myeloma cell lines (HMCLs) (n=15), and primary myeloma marrow samples at diagnosis (n=49) and at relapse (n=18)...
August 3, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28768481/piil-visualization-of-dna-methylation-and-gene-expression-data-in-gene-pathways
#20
Behrooz Torabi Moghadam, Neda Zamani, Jan Komorowski, Manfred Grabherr
BACKGROUND: DNA methylation is a major mechanism involved in the epigenetic state of a cell. It has been observed that the methylation status of certain CpG sites close to or within a gene can directly affect its expression, either by silencing or, in some cases, up-regulating transcription. However, a vertebrate genome contains millions of CpG sites, all of which are potential targets for methylation, and the specific effects of most sites have not been characterized to date. To study the complex interplay between methylation status, cellular programs, and the resulting phenotypes, we present PiiL, an interactive gene expression pathway browser, facilitating analyses through an integrated view of methylation and expression on multiple levels...
August 2, 2017: BMC Genomics
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