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histone modification chromatin cancer

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https://www.readbyqxmd.com/read/28092686/epigenomic-reprogramming-during-pancreatic-cancer-progression-links-anabolic-glucose-metabolism-to-distant-metastasis
#1
Oliver G McDonald, Xin Li, Tyler Saunders, Rakel Tryggvadottir, Samantha J Mentch, Marc O Warmoes, Anna E Word, Alessandro Carrer, Tal H Salz, Sonoko Natsume, Kimberly M Stauffer, Alvin Makohon-Moore, Yi Zhong, Hao Wu, Kathryn E Wellen, Jason W Locasale, Christine A Iacobuzio-Donahue, Andrew P Feinberg
During the progression of pancreatic ductal adenocarcinoma (PDAC), heterogeneous subclonal populations emerge that drive primary tumor growth, regional spread, distant metastasis, and patient death. However, the genetics of metastases largely reflects that of the primary tumor in untreated patients, and PDAC driver mutations are shared by all subclones. This raises the possibility that an epigenetic process might operate during metastasis. Here we report large-scale reprogramming of chromatin modifications during the natural evolution of distant metastasis...
January 16, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28089111/the-molecular-landscape-of-colitis-associated-carcinogenesis
#2
Deborah Saraggi, Matteo Fassan, Claudia Mescoli, Marco Scarpa, Nicola Valeri, Andrea Michielan, Renata D'Incá, Massimo Rugge
In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating role of longstanding/relapsing inflammatory insult on the intestinal mucosa, with the activation of different pro-inflammatory cytokines (TNF-α, IL-6, IL-10, IFN-γ), chemokines and metabolites of arachidonic acid resulting in the activation of key transcription factors such as NF-κB. Longstanding inflammation may also modify the intestinal microbiota, prompting the overgrowth of genotoxic microorganisms, which may act as further cancer promoters...
December 21, 2016: Digestive and Liver Disease
https://www.readbyqxmd.com/read/28073943/kdm4b-jmjd2b-is-a-p53-target-gene-that-modulates-the-amplitude-of-p53-response-after-dna-damage
#3
Laura Castellini, Eui Jung Moon, Olga V Razorenova, Adam J Krieg, Rie von Eyben, Amato J Giaccia
The p53 tumor suppressor protein plays a critical role in orchestrating the genomic response to various stress signals by acting as a master transcriptional regulator. Differential gene activity is controlled by transcription factors but also dependent on the underlying chromatin structure, especially on covalent histone modifications. After screening different histone lysine methyltransferases and demethylases, we identified JMJD2B/KDM4B as a p53-inducible gene in response to DNA damage. p53 directly regulates JMJD2B gene expression by binding to a canonical p53-consensus motif in the JMJD2B promoter...
January 9, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28067760/dna-methylation-targeting-the-dnmt-hmt-crosstalk-challenge
#4
REVIEW
Omar Castillo-Aguilera, Patrick Depreux, Ludovic Halby, Paola B Arimondo, Laurence Goossens
Chromatin can adopt a decondensed state linked to gene transcription (euchromatin) and a condensed state linked to transcriptional repression (heterochromatin). These states are controlled by epigenetic modulators that are active on either the DNA or the histones and are tightly associated to each other. Methylation of both DNA and histones is involved in either the activation or silencing of genes and their crosstalk. Since DNA/histone methylation patterns are altered in cancers, molecules that target these modifications are interesting therapeutic tools...
January 5, 2017: Biomolecules
https://www.readbyqxmd.com/read/28062403/mutated-chromatin-regulatory-factors-as-tumor-drivers-in-cancer
#5
REVIEW
Carl Koschmann, Felipe J Nunez, Flor Mendez, Jacqueline A Brosnan-Cashman, Alan K Meeker, Pedro R Lowenstein, Maria G Castro
Genes encoding proteins that regulate chromatin structure and DNA modifications [i.e., chromatin regulatory factors (CRF)] and genes encoding histone proteins harbor recurrent mutations in most human cancers. These mutations lead to modifications in tumor chromatin and DNA structure and an altered epigenetic state that contribute to tumorigenesis. Mutated CRFs have now been identified in most types of cancer and are increasingly regarded as novel therapeutic targets. In this review, we discuss DNA alterations in CRFs and how these influence tumor chromatin structure and function, which in turn leads to tumorigenesis...
January 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/28059591/epigenetic-modification-in-chromatin-machinery-and-its-deregulation-in-pediatric-brain-tumors-insight-into-epigenetic-therapies
#6
Eleonore Maury, Rintaro Hashizume
Malignancies are characterized by the reprogramming of epigenetic patterns. This reprogramming includes gains or losses in DNA methylation and disruption of normal patterns of covalent histone modifications, which are associated with changes in chromatin remodeling processes. This review will focus on the mechanisms underlying this reprogramming and, specifically, on the role of histone modification in chromatin machinery and the modifications in epigenetic processes occurring in brain cancer, with a specific focus on epigenetic therapies for pediatric brain tumors...
January 6, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28057213/a-new-molecular-mechanism-underlying-the-antitumor-effect-of-dna-methylation-inhibitors-via-an-antiviral-immune-response
#7
Y Saito, T Nakaoka, H Saito
Chromatin remodeling mediated by DNA methylation and histone modifications play critical roles in the transcriptional regulation of protein-coding genes, noncoding RNAs such as microRNAs, and endogenous retroviruses (ERVs). Many studies have shown that aberrant DNA methylation and histone modifications are associated with the initiation and progression of various malignancies. Epigenetic silencing of tumor suppressor genes in cancer is generally mediated by DNA hypermethylation of CpG island promoters and histone modifications such as histone deacetylation, methylation of histone H3 lysine 9 (H3K9), and trimethylation of H3K27...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/28054944/the-role-of-histone-protein-modifications-and-mutations-in-histone-modifiers-in-pediatric-b-cell-progenitor-acute-lymphoblastic-leukemia
#8
REVIEW
Szymon Janczar, Karolina Janczar, Agata Pastorczak, Hani Harb, Adam J W Paige, Beata Zalewska-Szewczyk, Marian Danilewicz, Wojciech Mlynarski
While cancer has been long recognized as a disease of the genome, the importance of epigenetic mechanisms in neoplasia was acknowledged more recently. The most active epigenetic marks are DNA methylation and histone protein modifications and they are involved in basic biological phenomena in every cell. Their role in tumorigenesis is stressed by recent unbiased large-scale studies providing evidence that several epigenetic modifiers are recurrently mutated or frequently dysregulated in multiple cancers. The interest in epigenetic marks is especially due to the fact that they are potentially reversible and thus druggable...
January 3, 2017: Cancers
https://www.readbyqxmd.com/read/28052018/targeting-micrornas-a-new-action-mechanism-of-natural-compounds
#9
REVIEW
Qian Lin, Leina Ma, Zhantao Liu, Zhihong Yang, Jin Wang, Jia Liu, Guohui Jiang
Unlike genetics, epigenetics involves the modification of genome without changes in DNA sequences, including DNA methylation, histone modification, chromatin remodeling and noncoding RNA regulation. MicroRNA (miRNA), a member of noncoding RNAs superfamily, participates in RNA interference through a unique mechanism. Currently, microRNAs have been found to be regulated by some natural compounds. Through altering the expression of miRNAs and influencing the downstream signaling pathways or target genes, several natural compounds exhibit its bioactivity in the prevention, diagnosis, therapy, prognosis and drug resistance of human diseases, such as cancer...
December 30, 2016: Oncotarget
https://www.readbyqxmd.com/read/27999365/alterations-of-epigenetic-regulators-in-pancreatic-cancer-and-their-clinical-implications
#10
REVIEW
Brittany R Silverman, Jiaqi Shi
Pancreatic cancer is one of the most aggressive human cancer types with a five-year survival less than 7%. Emerging evidence revealed that many genetic alterations in pancreatic cancer target epigenetic regulators. Some of these mutations are driver mutations in cancer development. Several most important mechanisms of epigenetic regulations include DNA methylation, histone modifications (methylation, acetylation, and ubiquitination), chromatin remodeling, and non-coding ribonucleic acids (RNAs). These modifications can alter chromatin structure and promoter accessibility, and thus lead to aberrant gene expression...
December 19, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27996159/persistent-phosphorylation-at-specific-h3-serine-residues-involved-in-chemical-carcinogen-induced-cell-transformation
#11
Xiaonian Zhu, Daochuan Li, Zhengbao Zhang, Wei Zhu, Wenxue Li, Jian Zhao, Xiumei Xing, Zhini He, Shan Wang, Fangping Wang, Lu Ma, Qing Bai, Xiaowen Zeng, Jie Li, Chen Gao, Yongmei Xiao, Qing Wang, Liping Chen, Wen Chen
Identification of aberrant histone H3 phosphorylation during chemical carcinogenesis will lead to a better understanding of the substantial roles of histone modifications in cancer development. To explore whether aberrant H3 phosphorylation contributes to chemical carcinogenesis, we examined the dynamic changes of H3 phosphorylation at various residues in chemical carcinogen-induced transformed human cells and human cancers. We found that histone H3 phosphorylation at Ser10 (p-H3S10) and Ser28 (p-H3S28) were up-regulated by 1...
December 20, 2016: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/27974677/histone-demethylase-lysine-demethylase-5b-in-development-and-cancer
#12
REVIEW
Mengjiao Han, Wenxia Xu, Pu Cheng, Hongchuan Jin, Xian Wang
Histone methylation is one of the most important chromatin posttranslational modifications. It has a range of influences on nuclear functions including epigenetic inheritance, transcriptional regulation and the maintenance of genome integrity. Changes in histone methylation status take part in various physiological and pathological processes. KDM5B (lysine demethylase 5B, also called JARID1B or PLU-1) encodes the histone H3 lysine4 (H3K4) demethylase and exhibits a strong transcriptional repression activity...
December 10, 2016: Oncotarget
https://www.readbyqxmd.com/read/27927750/mdm2-as-a-chromatin-modifier
#13
REVIEW
Magdalena Wienken, Ute M Moll, Matthias Dobbelstein
Mdm2 is the key negative regulator of the tumour suppressor p53, making it an attractive target for anti-cancer drug design. We recently identified a new role of Mdm2 in gene repression through its direct interaction with several proteins of the polycomb group (PcG) family. PcG proteins form polycomb repressive complexes PRC1 and PRC2. PRC2 (via EZH2) mediates histone 3 lysine 27 (H3K27) trimethylation, and PRC1 (via RING1B) mediates histone 2A lysine 119 (H2AK119) monoubiquitination. Both PRCs mostly support a compact and transcriptionally silent chromatin structure...
November 9, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27927666/epigenetic-biomarkers-in-progression-from-non-dysplastic-barrett-s-oesophagus-to-oesophageal-adenocarcinoma-a-systematic-review-protocol
#14
T Nieto, C L Tomlinson, J Dretzke, S Bayliss, M Dilworth, A D Beggs, O Tucker
INTRODUCTION: Barrett's oesophagus (BO), a metaplastic condition affecting the lower oesophagus due to long-standing gastro-oesophageal reflux and chronic inflammation, is a precursor lesion for oesophageal adenocarcinoma (OADC). There is no clinical test to predict which patients with BO will progress to OADC. The British Society of Gastroenterology recommends endoscopic surveillance of patients with BO. Epigenetic changes have been well characterised in the neoplastic progression of ulcerative colitis to colonic carcinoma, another gastrointestinal cancer associated with chronic inflammation...
December 7, 2016: BMJ Open
https://www.readbyqxmd.com/read/27926531/an-annotated-list-of-bivalent-chromatin-regions-in-human-es-cells-a-new-tool-for-cancer-epigenetic-research
#15
Franck Court, Philippe Arnaud
CpG islands (CGI) marked by bivalent chromatin in stem cells are believed to be more prone to aberrant DNA methylation in tumor cells. The robustness and genome-wide extent of this instructive program in different cancer types remain to be determined. To address this issue we developed a user-friendly approach to integrate the stem cell chromatin signature in customized DNA methylation analyses. We used publicly available ChIP-sequencing datasets of several human embryonic stem cell (hESC) lines to determine the extent of bivalent chromatin genome-wide...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899379/transcriptional-regulator-cnot3-defines-an-aggressive-colorectal-cancer-subtype
#16
Paloma Cejas, Alessia Cavazza, Chandri Yandava, Víctor Moreno, David Horst, Juan Moreno-Rubio, Emilio Burgos, Marta Mendiola, Len Taing, Ajay Goel, Jaime Feliu, Ramesh A Shivdasani
Cancer cells exhibit dramatic alterations of chromatin organization at cis-regulatory elements, but the molecular basis, extent and impact of these alterations are still being unraveled. Here we identify extensive genome-wide modification of sites bearing the active histone mark H3K4me2 in primary human colorectal cancers (CRC), as compared to corresponding benign precursor adenomas. Modification of certain CRC sites highlighted the activity of the transcription factor CNOT3, which is known to control self-renewal of embryonic stem cells (ESC)...
November 29, 2016: Cancer Research
https://www.readbyqxmd.com/read/27891192/the-quest-for-an-effective-and-safe-personalized-cell-therapy-using-epigenetic-tools
#17
REVIEW
T A L Brevini, G Pennarossa, E F M Manzoni, C E Gandolfi, A Zenobi, F Gandolfi
In the presence of different environmental cues that are able to trigger specific responses, a given genotype has the ability to originate a variety of different phenotypes. This property is defined as plasticity and allows cell fate definition and tissue specialization. Fundamental epigenetic mechanisms drive these modifications in gene expression and include DNA methylation, histone modifications, chromatin remodeling, and microRNAs. Understanding these mechanisms can provide powerful tools to switch cell phenotype and implement cell therapy...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27890923/the-epigenetic-landscape-of-renal-cancer
#18
REVIEW
Mark R Morris, Farida Latif
The majority of kidney cancers are associated with mutations in the von Hippel-Lindau gene and a small proportion are associated with infrequent mutations in other well characterized tumour-suppressor genes. In the past 15 years, efforts to uncover other key genes involved in renal cancer have identified many genes that are dysregulated or silenced via epigenetic mechanisms, mainly through methylation of promoter CpG islands or dysregulation of specific microRNAs. In addition, the advent of next-generation sequencing has led to the identification of several novel genes that are mutated in renal cancer, such as PBRM1, BAP1 and SETD2, which are all involved in histone modification and nucleosome and chromatin remodelling...
January 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27890782/bromodomain-histone-readers-and-cancer
#19
REVIEW
Abhinav K Jain, Michelle C Barton
Lysine acetylation of histone proteins is a fundamental post-translational modification that regulates chromatin structure and plays an important role in gene transcription. Aberrant levels of histone lysine acetylation are associated with the development of several diseases. Acetyl-lysine modifications create docking sites for bromodomains, which are structurally conserved modules present in transcription-associated proteins that are termed "reader" proteins. Bromodomain-containing reader proteins are part of multiprotein complexes that regulate transcription programs, which are often associated with profound phenotypic changes...
November 24, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27876760/changes-of-bivalent-chromatin-coincide-with-increased-expression-of-developmental-genes-in-cancer
#20
Stephan H Bernhart, Helene Kretzmer, Lesca M Holdt, Frank Jühling, Ole Ammerpohl, Anke K Bergmann, Bernd H Northoff, Gero Doose, Reiner Siebert, Peter F Stadler, Steve Hoffmann
Bivalent (poised or paused) chromatin comprises activating and repressing histone modifications at the same location. This combination of epigenetic marks at promoter or enhancer regions keeps genes expressed at low levels but poised for rapid activation. Typically, DNA at bivalent promoters is only lowly methylated in normal cells, but frequently shows elevated methylation levels in cancer samples. Here, we developed a universal classifier built from chromatin data that can identify cancer samples solely from hypermethylation of bivalent chromatin...
November 23, 2016: Scientific Reports
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