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histone modification chromatin cancer

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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/28323522/detection-of-cytosine-and-cpg-density-in-proto-oncogenes-and-tumor-suppressor-genes-in-promoter-sequences-of-acute-myeloid-leukemia
#2
Senol Dogan, Anis Cilic, Damir Marjanovic, Amina Kurtovic-Kozaric
Aberrant methylation is one of the driving forces of cancer genome development. Although the rate of methylation appears massively variable across the genome, it is mainly observed in histone modification, chromatin organization, DNA accessibility, or promoter sequence. Methylation of promoter sequence occurs mostly to cytosine nucleotides, which can affect transcription factors' binding affinities. In this study, we demonstrated that cytosine repeats (C types density), consisting of CC, CCC, CCCC, CCCCC, CCCCCC, CCCCCCC motifs and CpG islands density in 25 proto-oncogenes, tumor suppressor genes and control genes may play a role in the pathogenesis of acute myeloid leukemia...
March 21, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28315775/assessment-of-histone-tail-modifications-and-transcriptional-profiling-during-colon-cancer-progression-reveals-a-global-decrease-in-h3k4me3-activity
#3
Karen Triff, Mathew W McLean, Kranti Konganti, Jiahui Pang, Evelyn Callaway, Beiyan Zhou, Ivan Ivanov, Robert S Chapkin
During colon cancer, epigenetic alterations contribute to the dysregulation of major cellular functions and signaling pathways. Modifications in chromatin signatures such as H3K4me3 and H3K9ac, which are associated with transcriptionally active genes, can lead to genomic instability and perturb the expression of gene sets associated with oncogenic processes. In order to further elucidate early pre-tumorigenic epigenetic molecular events driving CRC, we integrated diverse, genome-wide, epigenetic inputs (by high throughput sequencing of RNA, H3K4me3, and H3K9ac) and compared differentially expressed transcripts (DE) and enriched regions (DER) in an in-vivo rat colon cancer progression model...
March 15, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28304185/modulation-of-transcription-factor-binding-and-epigenetic-regulation-of-the-mlh1-cpg-island-and-shore-by-polymorphism-rs1800734-in-colorectal-cancer
#4
Andrea J Savio, Bharati Bapat
The MLH1 promoter polymorphism rs1800734 is associated with MLH1 CpG island hypermethylation and expression loss in colorectal cancer (CRC). Conversely, variant rs1800734 is associated with MLH1 shore, but not island, hypomethylation in peripheral blood mononuclear cell DNA. To explore these distinct patterns, MLH1 CpG island and shore methylation was assessed in CRC cell lines stratified by rs1800734 genotype. Cell lines containing the variant A allele demonstrated MLH1 shore hypomethylation compared to wild type (GG)...
March 17, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28300602/yeats-domain-a-histone-acylation-reader-in-health-and-disease
#5
REVIEW
Dan Zhao, Yuanyuan Li, Xiaozhe Xiong, Zhonglei Chen, Haitao Li
Histone post-translational modifications (PTMs) carry an epigenetic layer of message to regulate diverse cellular processes at the chromatin level. Many of these PTMs are selectively recognized by dedicated effector proteins for normal cell growth and development, while dysregulation of these recognition events is often implicated in human diseases, notably cancer. Thus, it is fundamentally important to elucidate the regulatory mechanism(s) underlying readout of PTMs on histones. The YEATS domain is an emerging reader module that selectively recognizes histone lysine acylation with a preference for crotonylation over acetylation...
March 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28300060/h3-ubiquitination-by-nedd4-regulates-h3-acetylation-and-tumorigenesis
#6
Xian Zhang, Binkui Li, Abdol Hossein Rezaeian, Xiaohong Xu, Ping-Chieh Chou, Guoxiang Jin, Fei Han, Bo-Syong Pan, Chi-Yun Wang, Jie Long, Anmei Zhang, Chih-Yang Huang, Fuu-Jen Tsai, Chang-Hai Tsai, Christopher Logothetis, Hui-Kuan Lin
Dynamic changes in histone modifications under various physiological cues play important roles in gene transcription and cancer. Identification of new histone marks critical for cancer development is of particular importance. Here we show that, in a glucose-dependent manner, E3 ubiquitin ligase NEDD4 ubiquitinates histone H3 on lysine 23/36/37 residues, which specifically recruits histone acetyltransferase GCN5 for subsequent H3 acetylation. Genome-wide analysis of chromatin immunoprecipitation followed by sequencing reveals that NEDD4 regulates glucose-induced H3 K9 acetylation at transcription starting site and enhancer regions...
March 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28298630/proteomic-analysis-of-proteome-and-histone-post-translational-modifications-in-heat-shock-protein-90-inhibition-mediated-bladder-cancer-therapeutics
#7
Qingdi Quentin Li, Jian-Jiang Hao, Zheng Zhang, L Spencer Krane, Kai H Hammerich, Thomas Sanford, Jane B Trepel, Len Neckers, Piyush K Agarwal
Heat shock protein 90 (HSP90) inhibition is an attractive strategy for cancer treatment. Several HSP90 inhibitors have shown promising effects in clinical oncology trials. However, little is known about HSP90 inhibition-mediated bladder cancer therapy. Here, we report a quantitative proteomic study that evaluates alterations in protein expression and histone post-translational modifications (PTMs) in bladder carcinoma in response to HSP90 inhibition. We show that 5 HSP90 inhibitors (AUY922, ganetespib, SNX2112, AT13387, and CUDC305) potently inhibited the proliferation of bladder cancer 5637 cells in a dose- and time-dependent manner...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28266526/elf-mf-exposure-affects-the-robustness-of-epigenetic-programming-during-granulopoiesis
#8
Melissa Manser, Mohamad R Abdul Sater, Christoph D Schmid, Faiza Noreen, Manuel Murbach, Niels Kuster, David Schuermann, Primo Schär
Extremely-low-frequency magnetic fields (ELF-MF) have been classified as "possibly carcinogenic" to humans on the grounds of an epidemiological association of ELF-MF exposure with an increased risk of childhood leukaemia. Yet, underlying mechanisms have remained obscure. Genome instability seems an unlikely reason as the energy transmitted by ELF-MF is too low to damage DNA and induce cancer-promoting mutations. ELF-MF, however, may perturb the epigenetic code of genomes, which is well-known to be sensitive to environmental conditions and generally deranged in cancers, including leukaemia...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28241481/histone-h3-acetyl-k9-and-histone-h3-tri-methyl-k4-as-prognostic-markers-for-patients-with-cervical-cancer
#9
Susanne Beyer, Junyan Zhu, Doris Mayr, Christina Kuhn, Sandra Schulze, Simone Hofmann, Christian Dannecker, Udo Jeschke, Bernd P Kost
Chromatin remodeling alters gene expression in carcinoma tissue. Although cervical cancer is the fourth most common cancer in women worldwide, a systematic study about the prognostic value of specific changes in the chromatin structure, such as histone acetylation or histone methylation, is missing. In this study, the expression of histone H3 acetyl K9, which is known to denote active regions at enhancers and promoters, and histone H3 tri methyl K4, which preferentially identifies active gene promoters, were examined as both show high metastatic potential...
February 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28239551/genome-wide-chromatin-accessibility-dna-methylation-and-gene-expression-analysis-of-histone-deacetylase-inhibition-in-triple-negative-breast-cancer
#10
Matias A Bustos, Matthew P Salomon, Nellie Nelson, Sandy C Hsu, Maggie L DiNome, Dave S B Hoon, Diego M Marzese
Triple-negative breast cancer (TNBC), especially the subset with a basal phenotype, represents the most aggressive subtype of breast cancer. Unlike other solid tumors, TNBCs harbor a low number of driver mutations. Conversely, we and others have demonstrated a significant impact of epigenetic alterations, including DNA methylation and histone post-translational modifications, affecting TNBCs. Due to the promising results in pre-clinical studies, histone deacetylase inhibitors (HDACi) are currently being tested in several clinical trials for breast cancer and other solid tumors...
June 2017: Genomics Data
https://www.readbyqxmd.com/read/28212627/genome-wide-identification-of-direct-hbx-genomic-targets
#11
Francesca Guerrieri, Laura Belloni, Daniel D'Andrea, Natalia Pediconi, Loredana Le Pera, Barbara Testoni, Cecilia Scisciani, Oceane Floriot, Fabien Zoulim, Anna Tramontano, Massimo Levrero
BACKGROUND: The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV...
February 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28212444/sumo-modification-of-a-heterochromatin-histone-demethylase-jmjd2a-enables-viral-gene-transactivation-and-viral-replication
#12
Wan-Shan Yang, Mel Campbell, Pei-Ching Chang
Small ubiquitin-like modifier (SUMO) modification of chromatin has profound effects on transcription regulation. By using Kaposi's sarcoma associated herpesvirus (KSHV) as a model, we recently demonstrated that epigenetic modification of viral chromatin by SUMO-2/3 is involved in regulating gene expression and viral reactivation. However, how this modification orchestrates transcription reprogramming through targeting histone modifying enzymes remains largely unknown. Here we show that JMJD2A, the first identified Jumonji C domain-containing histone demethylase, is the histone demethylase responsible for SUMO-2/3 enrichment on the KSHV genome during viral reactivation...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28196596/chemosensitive-relapse-in-small-cell-lung-cancer-proceeds-through-an-ezh2-slfn11-axis
#13
Eric E Gardner, Benjamin H Lok, Valentina E Schneeberger, Patrice Desmeules, Linde A Miles, Paige K Arnold, Andy Ni, Inna Khodos, Elisa de Stanchina, Thuyen Nguyen, Julien Sage, John E Campbell, Scott Ribich, Natasha Rekhtman, Afshin Dowlati, Pierre P Massion, Charles M Rudin, John T Poirier
Small cell lung cancer is initially highly responsive to cisplatin and etoposide but in almost every case becomes rapidly chemoresistant, leading to death within 1 year. We modeled acquired chemoresistance in vivo using a series of patient-derived xenografts to generate paired chemosensitive and chemoresistant cancers. Multiple chemoresistant models demonstrated suppression of SLFN11, a factor implicated in DNA-damage repair deficiency. In vivo silencing of SLFN11 was associated with marked deposition of H3K27me3, a histone modification placed by EZH2, within the gene body of SLFN11, inducing local chromatin condensation and gene silencing...
February 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28177766/functional-assessment-of-mecp2-in-rett-syndrome-and-cancers-of-breast-colon-and-prostate
#14
Somnath Pandey, Kevin Pruitt
Ever since the first report that mutations in methyl-CpG-binding protein 2 (MeCP2) causes Rett syndrome (RTT), a severe neurological disorder in females world-wide, there has been a keen interest to gain a comprehensive understanding of this protein. While the classical model associated with MeCP2 function suggests its role in gene suppression via recruitment of co-repressor complexes and histone deacetylases to methylated CpG-sites, recent discoveries have brought to light its role in transcription activation, modulation of RNA splicing and chromatin compaction...
November 10, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28176655/epigenetics-in-clinical-management-of-children-and-adolescents-with-brain-tumors
#15
Andres Morales La Madrid, Mark W Kieran
Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages -not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the "classic" current therapeutic approaches...
February 3, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28166537/synthetic-essentiality-of-chromatin-remodelling-factor-chd1-in-pten-deficient-cancer
#16
Di Zhao, Xin Lu, Guocan Wang, Zhengdao Lan, Wenting Liao, Jun Li, Xin Liang, Jasper Robin Chen, Sagar Shah, Xiaoying Shang, Ming Tang, Pingna Deng, Prasenjit Dey, Deepavali Chakravarti, Peiwen Chen, Denise J Spring, Nora M Navone, Patricia Troncoso, Jianhua Zhang, Y Alan Wang, Ronald A DePinho
Synthetic lethality and collateral lethality are two well-validated conceptual strategies for identifying therapeutic targets in cancers with tumour-suppressor gene deletions. Here, we explore an approach to identify potential synthetic-lethal interactions by screening mutually exclusive deletion patterns in cancer genomes. We sought to identify 'synthetic-essential' genes: those that are occasionally deleted in some cancers but are almost always retained in the context of a specific tumour-suppressor deficiency...
February 23, 2017: Nature
https://www.readbyqxmd.com/read/28157208/rnf20-and-histone-h2b-ubiquitylation-exert-opposing-effects-in-basal-like-versus-luminal-breast-cancer
#17
Ohad Tarcic, Roy Z Granit, Ioannis S Pateras, Hadas Masury, Bella Maly, Yaara Zwang, Yosef Yarden, Vassilis G Gorgoulis, Eli Pikarsky, Ittai Ben-Porath, Moshe Oren
Breast cancer subtypes display distinct biological traits that influence their clinical behavior and response to therapy. Recent studies have highlighted the importance of chromatin structure regulators in tumorigenesis. The RNF20-RNF40 E3 ubiquitin ligase complex monoubiquitylates histone H2B to generate H2Bub1, while the deubiquitinase (DUB) USP44 can remove this modification. We found that RNF20 and RNF40 expression and global H2Bub1 are relatively low, and USP44 expression is relatively high, in basal-like breast tumors compared with luminal tumors...
February 3, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28139737/histone-h4-expression-is-cooperatively-maintained-by-ikk%C3%AE-and-akt1-which-attenuates-cisplatin-induced-apoptosis-through-the-dna-pk-rip1-iaps-signaling-cascade
#18
Ruixue Wang, Xuelian Zheng, Lei Zhang, Bin Zhou, Huaizhong Hu, Zhiping Li, Lin Zhang, Yong Lin, Xia Wang
While chromatin remodeling mediated by post-translational modification of histone is extensively studied in carcinogenesis and cancer cell's response to chemotherapy and radiotherapy, little is known about the role of histone expression in chemoresistance. Here we report a novel chemoresistance mechanism involving histone H4 expression. Extended from our previous studies showing that concurrent blockage of the NF-κB and Akt signaling pathways sensitizes lung cancer cells to cisplatin-induced apoptosis, we for the first time found that knockdown of Akt1 and the NF-κB-activating kinase IKKβ cooperatively downregulated histone H4 expression, which increased cisplatin-induced apoptosis in lung cancer cells...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28129645/epigenetic-alterations-of-gastrokine-1-gene-expression-in-gastric-cancer
#19
Filomena Altieri, Chiara Stella Di Stadio, Antonella Federico, Giuseppina Miselli, Maurizio De Palma, Emilia Rippa, Paolo Arcari
The gastrokine 1 (GKN1) protein is important for maintaining the physiological function of the gastric mucosa. GKN1 is down-regulated in gastric tumor tissues and derived cell lines and its over-expression in gastric cancer cells induces apoptosis, suggesting a possible role for the protein as a tumor suppressor. However, the mechanism by which GKN1 is inactivated in gastric cancer remains unknown. Here, we investigated the causes of GKN1 silencing to determine if epigenetic mechanisms such as histonic modification could contribute to its down-regulation...
January 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28125036/regulation-of-replication-fork-advance-and-stability-by-nucleosome-assembly
#20
REVIEW
Felix Prado, Douglas Maya
The advance of replication forks to duplicate chromosomes in dividing cells requires the disassembly of nucleosomes ahead of the fork and the rapid assembly of parental and de novo histones at the newly synthesized strands behind the fork. Replication-coupled chromatin assembly provides a unique opportunity to regulate fork advance and stability. Through post-translational histone modifications and tightly regulated physical and genetic interactions between chromatin assembly factors and replisome components, chromatin assembly: (1) controls the rate of DNA synthesis and adjusts it to histone availability; (2) provides a mechanism to protect the integrity of the advancing fork; and (3) regulates the mechanisms of DNA damage tolerance in response to replication-blocking lesions...
January 24, 2017: Genes
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