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Epigenetic silencing

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https://www.readbyqxmd.com/read/28326594/hypoacetylation-of-acetyl-histone-h3-h3k9ac-as-marker-of-poor-prognosis-in-oral-cancer
#1
Liana Preto Webber, Vivian Petersen Wagner, Marina Curra, Pablo Agustin Vargas, Luise Meurer, Vinícius Coelho Carrard, Cristiane Helena Squarize, Rogério Moraes Castilho, Manoela Domingues Martins
AIMS: Epigenetics refers to changes in cell characteristics that occur independently of modifications to the DNA sequence. Oral carcinogenesis is influenced by modifications in epigenetic mechanisms, including changes in histones, which are proteins that support chromatin remodeling for the dynamic regulation of gene expression and silencing. The dysregulation of histone acetylation can lead to the uncontrolled activity of different genes, thereby triggering events associated with malignant transformation...
March 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28320934/allele-specific-non-cg-dna-methylation-marks-domains-of-active-chromatin-in-female-mouse-brain
#2
Christopher L Keown, Joel B Berletch, Rosa Castanon, Joseph R Nery, Christine M Disteche, Joseph R Ecker, Eran A Mukamel
DNA methylation at gene promoters in a CG context is associated with transcriptional repression, including at genes silenced on the inactive X chromosome in females. Non-CG methylation (mCH) is a distinct feature of the neuronal epigenome that is differentially distributed between males and females on the X chromosome. However, little is known about differences in mCH on the active (Xa) and inactive (Xi) X chromosomes because stochastic X-chromosome inactivation (XCI) confounds allele-specific epigenomic profiling...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28319413/aberrant-promoter-hypermethylation-of-p16-survivin-and-retinoblastoma-in-gastric-cancer
#3
L Guo, C Huang, Q J Ji
BACKGROUND: Gastric cancer is common and can be found throughout the world. Notoriously like other cancers, gastric cancer is a consequence of cellular regulation disorder. Epigenetics, including many oncogenes or tumour suppressor genes, can provide some clues for this kind of disorder. DNA methylation, especially promoter methylation, which causes the silence/decrease of tumour related genes, has become a focus in various tumour types. The aim of this study was to investigate promoter methylation of certain genes: p16, survivin, retinoblastoma (Rb), all of which have been regarded as genes related to gastric cancer...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28318821/snf2-family-protein-fft3-suppresses-nucleosome-turnover-to-promote-epigenetic-inheritance-and-proper-replication
#4
Nitika Taneja, Martin Zofall, Vanivilasini Balachandran, Gobi Thillainadesan, Tomoyasu Sugiyama, David Wheeler, Ming Zhou, Shiv I S Grewal
Heterochromatin can be epigenetically inherited in cis, leading to stable gene silencing. However, the mechanisms underlying heterochromatin inheritance remain unclear. Here, we identify Fft3, a fission yeast homolog of the mammalian SMARCAD1 SNF2 chromatin remodeler, as a factor uniquely required for heterochromatin inheritance, rather than for de novo assembly. Importantly, we find that Fft3 suppresses turnover of histones at heterochromatic loci to facilitate epigenetic transmission of heterochromatin in cycling cells...
March 8, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28315733/wt1-ameliorates-podocyte-injury-via-repression-of-ezh2-%C3%AE-catenin-pathway-in-diabetic-nephropathy
#5
Jiao Wan, Xiaoyan Hou, Zhanmei Zhou, Jian Geng, Jianwei Tian, Jing Nie, Xiaoyan Bai
Epigenetic modulation of podocyte injury plays a pivotal role in diabetic nephropathy (DN). Wilm's tumor 1 (WT1) has been found to have opposing roles with β-catenin in podocyte biology. Herein, we asked whether the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) promotes WT1-induced podocyte injury via β-catenin activation and the underlying mechanisms. We found that WT1 antagonized EZH2 and ameliorated β-catenin-mediated podocyte injury as demonstrated by attenuated podocyte mesenchymal transition, maintenance of podocyte architectural integrity, decreased podocyte apoptosis and oxidative stress...
March 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28315662/insights-into-the-establishment-of-chromatin-states-in-pluripotent-cells-from-studies-of-x-inactivation
#6
REVIEW
Andreas Postlmayr, Anton Wutz
Animal development entails the sequential and coordinated specialisation of cells. During cell differentiation transcription factors, cell signalling pathways and chromatin associated protein complexes cooperate in regulating the expression of a large number of genes. Here we review the present understanding of the establishment of chromatin states by focusing on X chromosome inactivation (XCI) as a model for facultative heterochromatin formation in female embryonic cells. The inactive X chromosome (Xi) is large enough to be investigated by biochenical and microscopy techniques...
March 15, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28314692/identification-of-an-atypical-etiological-head-and-neck-squamous-carcinoma-subtype-featuring-the-cpg-island-methylator-phenotype
#7
K Brennan, J L Koenig, A J Gentles, J B Sunwoo, O Gevaert
Head and neck squamous cell carcinoma (HNSCC) is broadly classified into HNSCC associated with human papilloma virus (HPV) infection, and HPV negative HNSCC, which is typically smoking-related. A subset of HPV negative HNSCCs occur in patients without smoking history, however, and these etiologically 'atypical' HNSCCs disproportionately occur in the oral cavity, and in female patients, suggesting a distinct etiology. To investigate the determinants of clinical and molecular heterogeneity, we performed unsupervised clustering to classify 528 HNSCC patients from The Cancer Genome Atlas (TCGA) into putative intrinsic subtypes based on their profiles of epigenetically (DNA methylation) deregulated genes...
March 1, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28303350/immunohistochemical-evaluation-of-klotho-and-dna-methyltransferase-3a-in-oral-squamous-cell-carcinomas
#8
Bhoj Raj Adhikari, Osamu Uehara, Hirofumi Matsuoka, Rie Takai, Fumiya Harada, Masafumi Utsunomiya, Takatoshi Chujo, Tetsuro Morikawa, Mamata Shakya, Koki Yoshida, Jun Sato, Toshiya Arakawa, Michiko Nishimura, Hiroki Nagayasu, Itsuo Chiba, Yoshihiro Abiko
Carcinoma follows a course of multiple changes that are affected by several important factors, with epigenetic silencing of the promoter gene being one of them. A series of studies have suggested that epigenetic changes in the anti-aging gene Klotho may be one of the emerging areas of concern in the study of carcinogenesis. We hypothesized that epigenetic silencing of Klotho due to hypermethylation of DNMT3a may be one of the causes of carcinoma in the oral and maxillofacial region. In this study, we analyzed the immunohistochemical expressions of Klotho and DNMT3a in tissues obtained from oral dysplasia and oral squamous cell carcinoma...
March 16, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28302795/causal-role-for-inheritance-of-h3k27me3-in-maintaining-the-off-state-of-a-drosophila-hox-gene
#9
Rory T Coleman, Gary Struhl
Many eukaryotic cells can respond to transient environmental or developmental stimuli with heritable changes in gene expression that are associated with nucleosome modifications. However, it remains uncertain whether modified nucleosomes play a causal role in transmitting such epigenetic memories, as opposed to controlling or merely reflecting transcriptional states inherited by other means. Here, we provide in vivo evidence that H3K27 trimethylated nucleosomes, once established at a repressed Drosophila HOX gene, remain heritably associated with that gene and can carry the memory of the silenced state through multiple rounds of replication, even when the capacity to copy the H3K27me3 mark to newly incorporated nucleosomes is diminished or abolished...
March 16, 2017: Science
https://www.readbyqxmd.com/read/28302794/dna-sequence-dependent-epigenetic-inheritance-of-gene-silencing-and-histone-h3k9-methylation
#10
Xiaoyi Wang, Danesh Moazed
Epigenetic inheritance mechanisms play fundamental roles in maintaining cellular memory of gene expression states. In fission yeast, histone H3 lysine 9 (H3K9me) is methylated at heterochromatic domains. These domains can be epigenetically inherited when epi1+, encoding an enzyme that promotes H3K9 demethylation, is deleted. How native epigenetic states are stably maintained in epe1(+) cells remains unknown. Here, we developed a system to examine the role of DNA sequence and genomic context in propagation of a cis-heritable H3K9me-dependent silenced state...
March 16, 2017: Science
https://www.readbyqxmd.com/read/28302031/hif1a-is-overexpressed-in-medulloblastoma-and-its-inhibition-reduces-proliferation-and-increases-epas1-and-atg16l1-methylation
#11
Gustavo Alencastro Veiga Cruzeiro, Maristella Bergamo Dos Reis, Vanessa Silva Silveira, Régia Caroline Peixoto Lira, Carlos Gilberto Carlotti, Luciano Neder, Ricardo Santos Oliveira, José Andres Yunes, Silvia Regina Brandalise, Simone Aguiar, Agda Karina Eterovic, Luiz Gonzaga Tone, Carlos Alberto Scrideli, Elvis Terci Valera
BACKGROUND: Genetic and epigenetic modifications are closely related to tumor initiation and progression and can provide guidance for understanding tumor functioning, potentially leading to the discovery of new therapies. Studies have associated hypoxia-related genes to tumor progression and chemo/radioresistance in brain tumors. Information on the expression profile of hypoxia-related genes in pediatric medulloblastoma, although scarce, may reveal relevant information that could support treatment decisions...
March 15, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28298929/%C3%AE-arrestin1-mir-326-transcription-unit-is-epigenetically-regulated-in-neural-stem-cells-where-it-controls-stemness-and-growth-arrest
#12
Agnese Po, Federica Begalli, Luana Abballe, Vincenzo Alfano, Zein Mersini Besharat, Giuseppina Catanzaro, Alessandra Vacca, Maddalena Napolitano, Marco Tafani, Felice Giangaspero, Franco Locatelli, Elisabetta Ferretti, Evelina Miele
Cell development is regulated by a complex network of mRNA-encoded proteins and microRNAs, all funnelling onto the modulation of self-renewal or differentiation genes. How intragenic microRNAs and their host genes are transcriptionally coregulated and their functional relationships for the control of neural stem cells (NSCs) are poorly understood. We propose here the intragenic miR-326 and its host gene β-arrestin1 as novel players whose epigenetic silencing maintains stemness in normal cerebellar stem cells...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28298436/chromatin-remodeler-chd4-represses-aberrant-expression-of-tbx3-and-sustains-self-renewal-of-embryonic-stem-cells
#13
Haixin Zhao, Zhijun Han, Xinyuan Liu, Junjie Gu, Fan Tang, Gang Wei, Ying Jin
The unique properties of embryonic stem cells (ESCs), unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of a series of transcriptional factors and epigenetic modulators. However, molecular mechanisms underlying the function of these regulators are not fully elucidated. Chd4, an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs. However, its function in the regulation of ESC properties remains elusive...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28296507/lncrna-pvt1-epigenetically-silences-mir-195-and-modulates-emt-and-chemoresistance-in-cervical-cancer-cells
#14
Ching-Ju Shen, Ya-Min Cheng, Chiu-Lin Wang
The plasmacytoma variant translocation 1 gene (PVT1) is an oncogenic lncRNA with regulative effect on chemosensitivity in cervical cancer. However, the underlying mechanisms were not fully understood. In this study, HPV16 positive CaSki and SiHa cells were used as in-vitro cell model. Knockdown of HPV16 E7 significantly inhibited PVT1 and restored miR-195 expression. PVT1 directly interacts with EZH2 and the complex anchors in the promoter region of miR-195. PVT1 overexpression resulted in increased H3K27me3 levels in the miR-195 promoter region, while PVT1 knockdown decreased H3K27me3 levels in the promoter region...
March 15, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28291773/comprehensive-molecular-exploration-identified-promoter-dna-methylation-of-the-crbp1-gene-as-a-determinant-of-radiation-sensitivity-in-rectal-cancer
#15
K Yokoi, K Yamashita, S Ishii, T Tanaka, N Nishizawa, A Tsutsui, H Miura, H Katoh, T Yamanashi, M Naito, T Sato, T Nakamura, M Watanabe
BACKGROUND: Neoadjuvant chemoradiotherapy (NCRT) for advanced rectal cancer (RC) is a well-evidenced therapy; however, some RC patients have no therapeutic response. Patient selection for NCRT so that non-responsive patients are excluded has been subjective. To date, no molecular markers indicating radiation sensitivity have been reported. METHODS: We irradiated six colorectal cancer (CRC) cell lines and identified HCT116 cells as radiation-sensitive and HCT15 and DLD-1 cells as radiation resistant...
March 14, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28291253/mecp2-mediated-epigenetic-silencing-of-mir-137-contributes-to-colorectal-adenoma-carcinoma-sequence-and-tumor-progression-via-relieving-the-suppression-of-c-met
#16
Tao Chen, Shi-Lun Cai, Jian Li, Zhi-Peng Qi, Xu-Quan Li, Le-Chi Ye, Xiao-Feng Xie, Ying-Yong Hou, Li-Qing Yao, Mei-Dong Xu, Ping-Hong Zhou, Jian-Min Xu, Yun-Shi Zhong
The molecular mechanisms underlying colorectal cancer (CRC) development remain elusive. In this study, we examined the miRNA and mRNA expressions in the adenoma-carcinoma sequence (ACS), a critical neoplastic progression in CRC development. We found that miR-137 was down-regulated in all adenoma and carcinoma tissues. Low miR-137 levels were correlated negatively with tumor progression and metastasis. Then we identified the inhibition effect of the miR-137 in CRC development, both in CRC cell lines and mouse models...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286748/the-importance-of-rest-for-development-and-function-of-beta-cells
#17
REVIEW
David Martin, Anne Grapin-Botton
Beta cells are defined by the genes they express, many of which are specific to this cell type, and ensure a specific set of functions. Beta cells are also defined by a set of genes they should not express (in order to function properly), and these genes have been called forbidden genes. Among these, the transcriptional repressor RE-1 Silencing Transcription factor (REST) is expressed in most cells of the body, excluding most populations of neurons, as well as pancreatic beta and alpha cells. In the cell types where it is expressed, REST represses the expression of hundreds of genes that are crucial for both neuronal and pancreatic endocrine function, through the recruitment of multiple transcriptional and epigenetic co-regulators...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28281974/silencing-of-atp4b-of-atpase-h-k-transporting-beta-subunit-by-intragenic-epigenetic-alteration-in-human-gastric-cancer-cells
#18
Shuye Lin, Bonan Lin, Xiaoyue Wang, Yuanming Pan, Qing Xu, Jin-Shen He, Wanghua Gong, Rui Xing, Yuqi He, Lihua Guo, Youyong Lu, Ji Ming Wang, Jiaqiang Huang
The ATPase H+/K+ Transporting Beta Subunit (ATP4B) encodes the β subunit of the gastric H+, K+-ATPase, which controls gastric acid secretion and is therefore a target for acid reduction. Downregulation of ATP4B was recently observed in human gastric cancer (GC) without known mechanisms. In the present study, we demonstrated that ATP4B expression was decreased in human GC tissues and cell lines associated with DNA hypermethylation and histone hypoacetylation of histone H3 lysine 9 at its intragenic region close to the transcriptional start site...
March 13, 2017: Oncology Research
https://www.readbyqxmd.com/read/28281550/reduced-h3k27me3-expression-in-merkel-cell-polyoma-virus-positive-tumors
#19
Klaus J Busam, Melissa P Pulitzer, Daniel C Coit, Maria Arcila, Danielle Leng, Achim A Jungbluth, Thomas Wiesner
Merkel cell carcinoma is a primary cutaneous neuroendocrine carcinoma, which once metastatic is difficult to treat. Recent mutation analyses of Merkel cell carcinoma revealed a low number of mutations in Merkel cell polyomavirus-associated tumors, and a high number of mutations in virus-negative combined squamous cell and neuroendocrine carcinomas of chronically sun-damaged skin. We speculated that the paucity of mutations in virus-positive Merkel cell carcinoma may reflect a pathomechanism that depends on derangements of chromatin without alterations in the DNA sequence (epigenetic dysregulation)...
March 10, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28280564/methylation-of-avpr1a-in-the-cortex-of-wild-prairie-voles-effects-of-cpg-position-and-polymorphism
#20
M Okhovat, S M Maguire, S M Phelps
DNA methylation can cause stable changes in neuronal gene expression, but we know little about its role in individual differences in the wild. In this study, we focus on the vasopressin 1a receptor (avpr1a), a gene extensively implicated in vertebrate social behaviour, and explore natural variation in DNA methylation, genetic polymorphism and neuronal gene expression among 30 wild prairie voles (Microtus ochrogaster). Examination of CpG density across 8 kb of the locus revealed two distinct CpG islands overlapping promoter and first exon, characterized by few CpG polymorphisms...
January 2017: Royal Society Open Science
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