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https://www.readbyqxmd.com/read/28734945/the-epigenomic-revolution-in-breast-cancer-from-single-gene-to-genome-wide-next-generation-approaches
#1
REVIEW
Veronica Davalos, Anna Martinez-Cardus, Manel Esteller
From the first identification of aberrant DNA methylation in primary human tumors more than three decades ago, exponential progress in cancer epigenetics research has been made. For many years, cancer epigenetics studies relied on identification of DNA methylation and histone modifications at specific genes. These studies laid the foundation for the field and revealed the epigenetic alterations as hallmark of cancer, as well as the crucial role of epigenetic mechanisms in tumorigenesis. The introduction of next-generation sequencing and array-based technologies for analyzing epigenetic states has accelerated our understanding about cancer and nowadays have become potent tools in our fight against the disease...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28733487/the-stat4-mll1-epigenetic-axis-regulates-the-antimicrobial-functions-of-murine-macrophages
#2
William F Carson, Karen A Cavassani, Elyara M Soares, Soichiro Hirai, Nicolai A Kittan, Matthew A Schaller, Melissa M Scola, Amrita Joshi, Akihiro Matsukawa, David M Aronoff, Craig N Johnson, Yali Dou, Katherine A Gallagher, Steven L Kunkel
Macrophages are critical immune cells for the clearance of microbial pathogens and cellular debris from peripheral tissues. Macrophage inflammatory responses are governed by gene expression patterns, and these patterns are often subject to epigenetic control. Chromatin modifications, such as histone methylation, regulate gene accessibility in macrophages, and macrophage polarization is governed in part by the expression and function of chromatin-modifying enzymes. The histone methyltransferase mixed-lineage leukemia 1 (MLL1) preferentially modifies lysine residue 4 on the unstructured protein tail of histone H3...
July 21, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28733365/contrasting-determinants-of-mutation-rates-in-germline-and-soma
#3
Chen Chen, Hongjian Qi, Yufeng Shen, Joseph Pickrell, Molly Przeworski
Recent studies of somatic and germline mutations have led to the identification of a number of factors that influence point mutation rates, including CpG methylation, expression levels, replication timing and GC content. Intriguingly, some of the effects appear to differ between soma and germline: in particular, whereas mutation rates have been reported to decrease with expression levels in tumors, no clear effect has been detected in the germline. Distinct approaches were taken to analyze the data, however, so it is hard to know whether these apparent differences are real...
July 21, 2017: Genetics
https://www.readbyqxmd.com/read/28732347/histone-demethylase-jmjd2c-epigenetic-regulators-in-tumors
#4
REVIEW
Chengcheng Zhang, Zhongqi Wang, Qing Ji, Qi Li
Histone methylation is one of the major epigenetic modifications, and various histone methylases and demethylases participate in the epigenetic regulating. JMJD2C has been recently identified as one of the histone lysine demethylases. As one member of the Jumonji-C histone demethylase family, JMJD2C has the ability to demethylate tri- or di-methylated histone 3 and 2 in either K9 (lysine residue 9) or K36 (lysine residue 36) sites by an oxidative reaction, thereby affecting heterochromatin formation, genomic imprinting, X-chromosome inactivation, and transcriptional regulation of genes...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28730160/epigenetic-interactions-between-alcohol-and-cannabinergic-effects-focus-on-histone-modification-and-dna-methylation
#5
Tiyash Parira, Alejandra Laverde, Marisela Agudelo
Epigenetic studies have led to a more profound understanding of the mechanisms involved in chronic conditions. In the case of alcohol addiction, according to the National Institute on Alcohol Abuse and Alcoholism, 16 million adults suffer from Alcohol Use Disorders (AUDs). Even though therapeutic interventions like behavioral therapy and medications to prevent relapse are currently available, no robust cure exists, which stems from the lack of understanding the mechanisms of action of alcohol and the lack of development of precision medicine approaches to treat AUDs...
April 2017: Journal of Alcoholism and Drug Dependence
https://www.readbyqxmd.com/read/28727579/enhanced-anticancer-efficacy-of-histone-deacetyl-inhibitor-suberoylanilide-hydroxamic-acid-in-combination-with-a-phosphodiesterase-inhibitor-pentoxifylline-in-human-cancer-cell-lines-and-in-vivo-tumor-xenografts
#6
Saranya Nidhyanandan, Boreddy S Thippeswamy, Kottapalli B Chandrasekhar, Neetinkumar D Reddy, Nagaraj M Kulkarni, Kandasamy Karthikeyan, Farhin R Khan, Jayaprakash Raghul, Govindharajan Vijaykanth, Shridhar Narayanan
Vorinostat [suberoylanilide hydroxamic acid (SAHA)], a histone deacetylase inhibitor, shows limited clinical activity against solid tumors when used alone. The methyl xanthine drug, pentoxifylline (PENT), has been described to have antitumor properties. The aim of this study was to look for the enhanced anticancer activities of both agents when used in combination at doses lower than their respective efficacy dose when used alone. We investigated the antitumor potential of this novel combination in vitro and in vivo...
July 19, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28727015/triennial-growth-and-development-symposium-molecular-mechanisms-related-to-bovine-intramuscular-fat-deposition-in-the-longissimus-muscle
#7
M Baik, H J Kang, S J Park, S W Na, M Piao, S Y Kim, D M Fassah, Y S Moon
The intramuscular fat (IMF) content of the LM, also known as marbling, is particularly important in determining the price of beef in Korea, Japan, and the United States. Deposition of IMF is influenced by both genetic (e.g., breed, gender, and genotype) and nongenetic factors (e.g., castration, nutrition, stressors, animal weight, and age). Castration of bulls markedly increases deposition of IMF, resulting in improved beef quality. Here, we present a comparative gene expression approach between bulls and steers...
May 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28726978/analysis-of-the-substrate-specificity-of-factor-vii-activating-protease-fsap-and-design-of-specific-and-sensitive-peptide-substrates
#8
Emrah Kara, Dipankar Manna, Geir Åge Løset, Eric L Schneider, Charles S Craik, Sandip Kanse
Factor VII (FVII) activating protease (FSAP) is a circulating serine protease that is likely to be involved in a number of disease conditions such as stroke, atherosclerosis, liver fibrosis, thrombosis and cancer. To date, no systematic information is available about the substrate specificity of FSAP. Applying phage display and positional scanning substrate combinatorial library (PS-SCL) approaches we have characterised the specificity of FSAP towards small peptides. Results were evaluated in the context of known protein substrates as well as molecular modelling of the peptides in the active site of FSAP...
July 20, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28725537/the-emerging-role-of-histone-demethylases-in-renal-cell-carcinoma
#9
REVIEW
Xiaoqiang Guo, Qiaoxia Zhang
Renal cell carcinoma (RCC), the most common kidney cancer, is responsible for more than 100,000 deaths per year worldwide. The molecular mechanism of RCC is poorly understood. Many studies have indicated that epigenetic changes such as DNA methylation, noncoding RNAs, and histone modifications are central to the pathogenesis of cancer. Histone demethylases (KDMs) play a central role in histone modifications. There is emerging evidence that KDMs such as KDM3A, KDM5C, KDM6A, and KDM6B play important roles in RCC...
2017: Journal of Kidney Cancer and VHL
https://www.readbyqxmd.com/read/28723896/maternal-h3k27me3-controls-dna-methylation-independent-imprinting
#10
Azusa Inoue, Lan Jiang, Falong Lu, Tsukasa Suzuki, Yi Zhang
Mammalian sperm and oocytes have different epigenetic landscapes and are organized in different fashions. After fertilization, the initially distinct parental epigenomes become largely equalized with the exception of certain loci, including imprinting control regions. How parental chromatin becomes equalized and how imprinting control regions escape from this reprogramming is largely unknown. Here we profile parental allele-specific DNase I hypersensitive sites in mouse zygotes and morula embryos, and investigate the epigenetic mechanisms underlying these allelic sites...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723643/methyltransferase-g9a-promotes-cervical-cancer-angiogenesis-and-decreases-patient-survival
#11
Ruey-Jien Chen, Chia-Tung Shun, Men-Luh Yen, Chia-Hung Chou, Ming-Chieh Lin
Research suggests that the epigenetic regulator G9a, a H3K9 histone methyltransferase, is involved in cancer invasion and metastasis. Here we show that G9a is linked to cancer angiogenesis and poor patient survival. Invasive cervical cancer has a higher G9a expression than cancer precursors or normal epithelium. Pharmacological inhibition and genetic silencing of G9a suppresses H3K9 methylation, cancer cell proliferation, angiogenesis, and cancer cell invasion/migration, but not apoptosis. Microarray and quantitative reverse transcription polymerase chain reaction analyses reveal that G9a induces a cohort of angiogenic factors that include angiogenin, interleukin-8, and C-X-C motif chemokine ligand 16...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723619/a-novel-sharpin-prmt5-h3r2me1-axis-is-essential-for-lung-cancer-cell-invasion
#12
Tingxiong Fu, Xiuwei Lv, Qingzhi Kong, Changjing Yuan
SHARPIN (Shank-associated RH domain interacting protein) is the main component of the linear ubiquitin chain activation complex (LUBAC). SHARPIN is involved in regulating inflammation and cancer progression. However, whether SHARPIN plays an important role in lung cancer metastasis and the potential underlying mechanism are still unknown. Here, for the first time, we reported that SHARPIN expression is closely related to lung cancer progression. Moreover, SHARPIN plays a central role in controlling lung cancer cell metastasis...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723559/kmt2a-and-kmt2b-mediate-memory-function-by-affecting-distinct-genomic-regions
#13
Cemil Kerimoglu, M Sadman Sakib, Gaurav Jain, Eva Benito, Susanne Burkhardt, Vincenzo Capece, Lalit Kaurani, Rashi Halder, Roberto Carlos Agís-Balboa, Roman Stilling, Hendrik Urbanke, Andrea Kranz, A Francis Stewart, Andre Fischer
Kmt2a and Kmt2b are H3K4 methyltransferases of the Set1/Trithorax class. We have recently shown the importance of Kmt2b for learning and memory. Here, we report that Kmt2a is also important in memory formation. We compare the decrease in H3K4 methylation and de-regulation of gene expression in hippocampal neurons of mice with knockdown of either Kmt2a or Kmt2b. Kmt2a and Kmt2b control largely distinct genomic regions and different molecular pathways linked to neuronal plasticity. Finally, we show that the decrease in H3K4 methylation resulting from Kmt2a knockdown partially recapitulates the pattern previously reported in CK-p25 mice, a model for neurodegeneration and memory impairment...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28722229/a-transposon-directed-epigenetic-change-in-zmcct-underlies-quantitative-resistance-to-gibberella-stalk-rot-in-maize
#14
Chao Wang, Qin Yang, Weixiang Wang, Yipu Li, Yanling Guo, Dongfeng Zhang, Xuena Ma, Wei Song, Jiuran Zhao, Mingliang Xu
A major resistance quantitative trait locus, qRfg1, significantly enhances maize resistance to Gibberella stalk rot, a devastating disease caused by Fusarium graminearum. However, the underlying molecular mechanism remains unknown. We adopted a map-based cloning approach to identify the resistance gene at qRfg1 and examined the dynamic epigenetic changes during qRfg1-mediated maize resistance to the disease. A CCT domain-containing gene, ZmCCT, is the causal gene at the qRfg1 locus and a polymorphic CACTA-like transposable element (TE1) c...
July 19, 2017: New Phytologist
https://www.readbyqxmd.com/read/28720588/ews-fli-is-a-master-regulator-of-metabolic-reprogramming-in-ewing-sarcoma
#15
Jason M Tanner, Claire Bensard, Peng Wei, Nathan M Krah, John C Schell, Jamie D Gardiner, Joshua D Schiffman, Stephen L Lessnick, Jared Rutter
Ewing sarcoma is a bone malignancy driven by a translocation event resulting in the fusion protein EWS/FLI1 (EF). EF functions as an aberrant and oncogenic transcription factor that misregulates the expression of thousands of genes. Previous work has focused principally on determining important transcriptional targets of EF, as well as characterizing important regulatory partnerships in EF-dependent transcriptional programs. Less is known, however, about EF-dependent metabolic changes or their role in Ewing sarcoma biology...
July 18, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28720579/recruitment-of-histone-modifications-to-assist-mrna-dosage-maintenance-after-degeneration-of-cytosine-dna-methylation-during-animal-evolution
#16
Andrew Yf Chang, Ben-Yang Liao
Following gene duplication, mRNA expression of the duplicated gene is reduced to maintain mRNA dosage. In mammals, this process is achieved with increased cytosine DNA methylation of the promoters of duplicated genes to suppress transcriptional initiation. However, not all animal species possess a full apparatus for cytosine DNA methylation. For such species such as roundworm (Caenorhabditis elegans, "worm" hereafter) or fruit fly (Drosophila melanogaster, "fly" hereafter), it is unclear how reduced expression of duplicated genes has been achieved evolutionarily...
July 18, 2017: Genome Research
https://www.readbyqxmd.com/read/28718400/histone-h3g34r-mutation-causes-replication-stress-homologous-recombination-defects-and-genomic-instability-in-s-pombe
#17
Rajesh K Yadav, Carolyn M Jablonowski, Alfonso G Fernandez, Brandon R Lowe, Ryan A Henry, David Finkelstein, Kevin J Barnum, Alison L Pidoux, Yin-Ming Kuo, Jie Huang, Matthew J O'Connell, Andrew J Andrews, Arzu Onar-Thomas, Robin C Allshire, Janet F Partridge
Recurrent somatic mutations of H3F3A in aggressive pediatric high-grade gliomas generate K27M or G34R/V mutant histone H3.3. H3.3-G34R/V mutants are common in tumors with mutations in p53 and ATRX, an H3.3-specific chromatin remodeler. To gain insight into the role of H3-G34R, we generated fission yeast that express only the mutant histone H3. H3-G34R specifically reduces H3K36 tri-methylation and H3K36 acetylation, and mutants show partial transcriptional overlap with set2 deletions. H3-G34R mutants exhibit genomic instability and increased replication stress, including slowed replication fork restart, although DNA replication checkpoints are functional...
July 18, 2017: ELife
https://www.readbyqxmd.com/read/28718376/riz1-and-histone-methylation-status-in-pituitary-adenomas
#18
Yake Xue, Ruokun Chen, Wei Du, Fengdong Yang, Xinting Wei
RIZ1 displays strong tumor-suppressive activities, which has a potential histone methyltransferase activity. The objective of the study was to evaluate the level and the methylation status of RIZ1 and analyze its association with clinicopathological features and the histone in the pituitary adenomas. We found that RIZ1-positive cases were 11/50 and H-Scores 22.75 ± 11.83 in invasive pituitary adenomas and 26/53 and 66.3 ± 21.7 in non-invasive pituitary adenomas (χ(2) = 8.182, p = 0.004). RIZ1 and C-myc showed the opposite trend in these cases...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28717873/orchestration-of-h3k27-methylation-mechanisms-and-therapeutic-implication
#19
REVIEW
Mei-Ren Pan, Ming-Chuan Hsu, Li-Tzong Chen, Wen-Chun Hung
Histone proteins constitute the core component of the nucleosome, the basic unit of chromatin. Chemical modifications of histone proteins affect their interaction with genomic DNA, the accessibility of recognized proteins, and the recruitment of enzymatic complexes to activate or diminish specific transcriptional programs to modulate cellular response to extracellular stimuli or insults. Methylation of histone proteins was demonstrated 50 years ago; however, the biological significance of each methylated residue and the integration between these histone markers are still under intensive investigation...
July 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28715960/histone-methylation-by-set-domain-proteins-in-fungi
#20
Michael Freitag
Histone-modifying enzymes are responsible for regulating transcription, recombination, DNA repair, DNA replication, chromatid cohesion, and chromosome segregation. Fungi are ideally suited for comparative chromatin biology because sequencing of numerous genomes from many clades is coupled to existing rich methodology that allows truly holistic approaches, integrating evolutionary biology with mechanistic molecular biology and ecology, promising applications in medicine or plant pathology. While genome information is rich, mechanistic studies on histone modifications are largely restricted to two yeasts, Saccharomyces cerevisiae and Schizosaccharomyces pombe, and one filamentous fungus, Neurospora crassa-three species that arguably are not representative of this diverse kingdom...
July 17, 2017: Annual Review of Microbiology
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