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https://www.readbyqxmd.com/read/28109165/melatonin-and-sirtuins-a-not-so-unexpected-relationship
#1
Juan C Mayo, Rosa M Sainz, Pedro González Menéndez, Vanesa Cepas, Dun-Xian Tan, Russel J Reiter
Epigenetic modifications, including methylation or acetylation as well as posttranscriptional modifications are mechanisms used by eukaryotic cells to increase the genome diversity in terms of differential gene expression and protein diversity. Among these modifying enzymes, sirtuins, a class III histone deacetylase (HDAC) enzymes are of particular importance. Sirtuins regulate the cell cycle, DNA repair, cell survival and apoptosis, thus having important roles in normal and cancer cells. Sirtuins can also regulate metabolic pathways by changing preference for glycolysis under aerobic conditions as well as glutaminolysis...
January 21, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28108626/a-new-role-for-er%C3%AE-silencing-via-dna-methylation-of-basal-stem-cell-and-emt-genes
#2
Eric A Ariazi, John C Taylor, Michael A Black, Emmanuelle Nicolas, Michael J Slifker, Diana J Azzam, Jeff Boyd
: Resistance to hormonal therapies is a major clinical problem in the treatment of estrogen receptor α-positive (ERα(+)) breast cancers. Epigenetic marks, namely DNA methylation of cytosine at specific CpG sites (5mCpG), are frequently associated with ERα(+) status in human breast cancers. Therefore, ERα may regulate gene expression in part via DNA methylation. This hypothesis was evaluated using a panel of breast cancer cell line models of antiestrogen resistance. Microarray gene expression profiling was used to identify genes normally silenced in ERα(+) cells but derepressed upon exposure to the demethylating agent decitabine, derepressed upon long-term loss of ERα expression, and resuppressed by gain of ERα activity/expression...
November 15, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108556/confirmation-of-five-novel-susceptibility-loci-for-systemic-lupus-erythematosus-sle-and-integrated-network-analysis-of-82-sle-susceptibility-loci
#3
Julio E Molineros, Wanling Yang, Xu-Jie Zhou, Celi Sun, Yukinori Okada, Huoru Zhang, Kek Heng Chua, Yu-Lung Lau, Yuta Kochi, Akari Suzuki, Kazuhiko Yamamoto, Jianyang Ma, So-Young Bang, Hye-Soon Lee, Kwangwoo Kim, Sang-Cheol Bae, Hong Zhang, Nan Shen, Loren L Looger, Swapan K Nath
We recently identified ten novel SLE susceptibility loci in Asians and uncovered several additional suggestive loci requiring further validation. This study aimed to replicate five of these suggestive loci in a Han Chinese cohort from Hong Kong, followed by meta-analysis (11,656 cases and 23,968 controls) on previously reported Asian and European populations, and perform bioinformatic analyses on all 82 reported SLE loci to identify shared regulatory signatures. We performed a battery of analyses for these five loci, as well as joint analyses on all 82 SLE loci...
January 20, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28108450/netland-quantitative-modeling-and-visualization-of-waddington-s-epigenetic-landscape-using-probabilistic-potential
#4
Jing Guo, Feng Lin, Xiaomeng Zhang, Vivek Tanavde, Jie Zheng
: Waddington's epigenetic landscape is a powerful metaphor for cellular dynamics driven by gene regulatory networks. Its quantitative modeling and visualization, however, remains a challenge, especially when there are more than two genes in the network. A software tool for Waddington's landscape has not been available in the literature. We present NetLand, an open-source software tool for modeling and simulating the kinetic dynamics of gene regulatory networks (GRNs), and visualizing the corresponding Waddington's epigenetic landscape in three dimensions without restriction on the number of genes in a GRN...
January 19, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28108419/regulation-of-protein-kinase-c-related-kinase-prk-signalling-by-the-tp%C3%AE-and-tp%C3%AE-isoforms-of-the-human-thromboxane-a2-receptor-implications-for-thromboxane-and-androgen-dependent-neoplastic-and-epigenetic-responses-in-prostate-cancer
#5
Aine G O'Sullivan, Eamon P Mulvaney, B Therese Kinsella
The prostanoid thromboxane (TX) A2 and its T Prostanoid receptor (the TP) are increasingly implicated in prostate cancer (PCa). Mechanistically, we recently discovered that both TPα and TPβ form functional signalling complexes with members of the protein kinase C-related kinase (PRK) family, AGC- kinases essential for the epigenetic regulation of androgen receptor (AR)-dependent transcription and promising therapeutic targets for treatment of castrate-resistant prostate cancer (CRPC). Critically, similar to androgens, activation of the PRKs through the TXA2/TP signalling axis induces phosphorylation of histone H3 at Thr11 (H3Thr11), a marker of androgen-induced chromatin remodelling and transcriptional activation, raising the possibility that TXA2-TP signalling can mimic and/or enhance AR-induced cellular changes even in the absence of circulating androgens such as in CRPC...
January 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28108348/epigenetic-basis-of-cancer-health-disparities-looking-beyond-genetic-differences
#6
REVIEW
Aamir Ahmad, Shafquat Azim, Haseeb Zubair, Mohammad Aslam Khan, Seema Singh, James E Carter, Rodney Rocconi, Ajay P Singh
Despite efforts at various levels, racial health disparities still exist in cancer patients. These inequalities in incidence and/or clinical outcome can only be explained by a multitude of factors, with genetic basis being one of them. Several investigations have provided convincing evidence to support epigenetic regulation of cancer-associated genes, which results in the differential transcriptome and proteome, and may be linked to a pre-disposition of individuals of certain race/ethnicity to early or more aggressive cancers...
January 17, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28108335/tryptase-catalyzed-core-histone-truncation-a-novel-epigenetic-regulatory-mechanism-in-mast-cells
#7
Fabio R Melo, Ola Wallerman, Aida Paivandy, Gabriela Calounova, Ann-Marie Gustafson, Benjamin R Sabari, Giuliano Zabucchi, C David Allis, Gunnar Pejler
BACKGROUND: Mast cells are key effector cells in allergic reactions. When activated to degranulate, they release a plethora of bioactive compounds from their secretory granules, including mast cell-restricted proteases such as tryptase. In a previous study we showed that tryptase, in addition to its intragranular location, can be found within the nuclei of mast cells where it truncates core histones at their N-terminal ends. OBJECTIVE: Considering that the N-terminal portions of the core histones constitute sites for posttranslational modifications of major epigenetic impact, we here evaluated whether histone truncation by tryptase could have an impact on epigenetic events in mast cells...
January 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28107481/bet-inhibitors-disrupt-rad21-dependent-conformational-control-of-kshv-latency
#8
Horng-Shen Chen, Alessandra De Leo, Zhuo Wang, Andrew Kerekovic, Robert Hills, Paul M Lieberman
Kaposi's Sarcoma-associated Herpesvirus (KSHV) establishes stable latent infection in B-lymphocytes and pleural effusion lymphomas (PELs). During latency, the viral genome persists as an epigenetically constrained episome with restricted gene expression programs. To identify epigenetic regulators of KSHV latency, we screened a focused small molecule library containing known inhibitors of epigenetic factors. We identified JQ1, a Bromodomain and Extended Terminal (BET) protein inhibitor, as a potent activator of KSHV lytic reactivation from B-cells carrying episomal KSHV...
January 20, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28107248/how-mice-are-indispensable-for-understanding-obesity-and-diabetes-genetics
#9
Alan D Attie, Gary A Churchill, Joseph H Nadeau
PURPOSE OF REVIEW: The task of cataloging human genetic variation and its relation to disease is rapidly approaching completion. The new challenge is to discover the function of disease-associated genes and to understand the pathways that lead to human disease. We propose that achieving this new level of understanding will increasingly rely on the use of model organisms. We discuss the advantages of the mouse as a model organism. RECENT FINDINGS: The collection of available mouse strains represents as much genetic and phenotype variation as is found in the human population...
January 19, 2017: Current Opinion in Endocrinology, Diabetes, and Obesity
https://www.readbyqxmd.com/read/28106784/microrna-29a-alleviates-bile-duct-ligation-exacerbation-of-hepatic-fibrosis-in-mice-through-epigenetic-control-of-methyltransferases
#10
Ya-Ling Yang, Feng-Sheng Wang, Sung-Chou Li, Mao-Meng Tiao, Ying-Hsien Huang
MicroRNA-29 (miR-29) is found to modulate hepatic stellate cells' (HSCs) activation and, thereby, reduces liver fibrosis pathogenesis. Histone methyltransferase regulation of epigenetic reactions reportedly participates in hepatic fibrosis. This study is undertaken to investigate the miR-29a regulation of the methyltransferase signaling and epigenetic program in hepatic fibrosis progression. miR-29a transgenic mice (miR-29aTg mice) and wild-type littermates were subjected to bile duct-ligation (BDL) to develop cholestatic liver fibrosis...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106510/a-drive-in-suvs-from-development-to-disease
#11
Vinay Kumar Rao, Ananya Pal, Reshma Taneja
Progression of cells through distinct phases of the cell cycle, and transition into out-of-cycling states, such as terminal differentiation and senescence, is accompanied by specific patterns of gene expression. These cell fate decisions are mediated not only by distinct transcription factors, but also chromatin modifiers that establish heritable epigenetic patterns. Lysine methyltransferases (KMTs) that mediate methylation marks on histone and non-histone proteins are now recognized as important regulators of gene expression in cycling and non-cycling cells...
January 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28106509/potential-epigenetic-biomarkers-of-obesity-related-insulin-resistance-in-human-whole-blood
#12
Samantha E Day, Richard L Coletta, Joon Young Kim, Luis A Garcia, Latoya E Campbell, Tonya R Benjamin, Lori R Roust, Elena A De Filippis, Lawrence J Mandarino, Dawn K Coletta
Obesity can increase the risk of complex metabolic diseases, including insulin resistance. Moreover, obesity can be caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are not well defined. Therefore, the identification of novel epigenetic biomarkers of obesity allows for a more complete understanding of the disease and its underlying insulin resistance. The aim of our study was to identify DNA methylation changes in whole-blood that were strongly associated with obesity and insulin resistance...
January 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28106467/follicular-lymphoma-a-b-cell-malignancy-addicted-to-epigenetic-mutations
#13
Koorosh Korfi, Sara Ali, James A Heward, Jude Fitzgibbon
While follicular lymphoma (FL) is exquisitely responsive to immuno-chemotherapy, many patients follow a relapsing remitting clinical course driven in part by a common precursor cell (CPC) population. Advances in next generation sequencing have provided valuable insights into the genetic landscape of FL and its clonal evolution in response to therapy, implicating perturbations of epigenetic regulators as a hallmark of the disease. Recurrent mutations of histone modifiers KMT2D, CREBBP, EP300, EZH2, ARIDIA, and linker histones are likely early events arising in the CPC pool, rendering epigenetic based therapies conceptually attractive for treatment of indolent and transformed FL...
January 20, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28106288/nuclear-inositide-signaling-via-phospholipase-c
#14
Stefano Ratti, Sara Mongiorgi, Giulia Ramazzotti, Matilde Y Follo, Giulia A Mariani, Pann-Ghill Suh, James A McCubrey, Lucio Cocco, Lucia Manzoli
The existence of an independent nuclear inositide pathway distinct from the cytoplasmic one has been demonstrated in different physiological systems and in diseases. In this prospect we analyze the role of PI-PLCβ1 nuclear isoform in relation to the cell cycle regulation, the cell differentiation and different physiopathological pathways focusing on the importance of the nuclear localization from both molecular and clinical point of view. PI-PLCβ1 is essential for G1/S transition through DAG and Cyclin D3 and plays also a central role in G2/M progression through Cyclin B1 and PKCα...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106010/models-of-life-epigenetics-diversity-cycles
#15
Kim Sneppen
This review emphasize aspects of biology that can be understood through repeated applications of simple causal rules. The selected topics include perspectives on gene regulation, phage lambda development, epigenetics, microbial ecology, as well as model approaches to diversity and punctuated equilibrium in evolution. Two outstanding features are repeatedly described. One is minimal rules to sustain specific states of a complex systems for a long time. The other is the collapse of such states and the subsequent dynamical cycle of situations that later return to new metastable states...
January 20, 2017: Reports on Progress in Physics
https://www.readbyqxmd.com/read/28105934/charm-discovery-of-combinatorial-chromatin-modification-patterns-in-hepatitis-b-virus-x-transformed-mouse-liver-cancer-using-association-rule-mining
#16
Sung Hee Park, Sun-Min Lee, Young-Joon Kim, Sangsoo Kim
BACKGROUND: Various chromatin modifications, identified in large-scale epigenomic analyses, are associated with distinct phenotypes of different cells and disease phases. To improve our understanding of these variations, many computational methods have been developed to discover novel sites and cell-specific chromatin modifications. Despite the availability of existing methods, there is still room for further improvement when they are applied to resolve the histone code hypothesis. Hence, we aim to investigate the development of a computational method to provide new insights into de novo combinatorial pattern discovery of chromatin modifications to characterize epigenetic variations in distinct phenotypes of different cells...
December 13, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28105774/stiffness-controlled-thermoresponsive-hydrogels-for-cell-harvesting-with-sustained-mechanical-memory
#17
Xingliang Fan, Lu Zhu, Ke Wang, Bingjie Wang, Yaozu Wu, Wei Xie, Chengyu Huang, Barbara Pui Chan, Yanan Du
Most mechanobiological investigations focused on in situ mechanical regulation of cells on stiffness-controlled substrates with few downstream applications, as it is still challenging to harvest and expand mechanically primed cells by enzymatic digestion (e.g., trypsin) without interrupting cellular mechanical memory between passages. This study develops thermoresponsive hydrogels with controllable stiffness to generate mechanically primed cells with intact mechanical memory for augmented wound healing. No significant cellular property alteration of the fibroblasts primed on thermoresponsive hydrogels with varied stiffness has been observed through thermoresponsive harvesting...
January 20, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28105729/whole-genome-grey-and-white-matter-dna-methylation-profiles-in-dorsolateral-prefrontal-cortex
#18
Jose Vicente Sanchez-Mut, Holger Heyn, Enrique Vidal, Raúl Delgado-Morales, Sebastian Moran, Sergi Sayols, Juan Sandoval, Isidre Ferrer, Manel Esteller, Johannes Gräff
The brain's neocortex is anatomically organized into grey and white matter, which are mainly composed by neuronal and glial cells, respectively. The neocortex can be further divided in different Brodmann areas according to their cytoarchitectural organization, which are associated with distinct cortical functions. There is increasing evidence that brain development and function are governed by epigenetic processes, yet their contribution to the functional organization of the neocortex remains incompletely understood...
January 20, 2017: Synapse
https://www.readbyqxmd.com/read/28105693/epigenetic-regulation-of-wnt-%C3%AE-catenin-signal-associated-genes-in-gastric-neoplasia-of-the-fundic-gland-chief-cell-predominant-type
#19
Takashi Murakami, Hiroyuki Mitomi, Takashi Yao, Tsuyoshi Saito, Tomoyoshi Shibuya, Sumio Watanabe
Gastric neoplasia of the fundic gland (chief cell-predominant) type (GNCCP) is a rare variant of gastric tumor. This tumor is associated with activation of the Wnt/β-catenin signaling pathway; however, the mechanisms underlying this activation remain unknown. To elucidate potential roles of Wnt/β-catenin signal-associated gene methylation in GNCCP, we performed β-catenin immunostaining and methylation-specific polymerase chain reaction (PCR) for their associated genes, including SFRPs, APC, AXIN2, and MCC, in 26 GNCCPs [i...
January 20, 2017: Pathology International
https://www.readbyqxmd.com/read/28105334/chronic-kidney-disease-in-children-and-the-role-of-epigenetics-future-therapeutic-trajectories
#20
Samuel N Uwaezuoke, Henrietta U Okafor, Vivian N Muoneke, Odutola I Odetunde, Chioma L Odimegwu
Global differences in the observed causes of chronic kidney disease (CKD) in children are well documented and are attributed to dissimilarities in clime, race, hereditary, and ancestry. Thus, familial clustering and disparities in CKD prevalence rates across ethnic and racial groups indicate that the progression of renal disease has a strong genetic component. Mammalian studies have demonstrated a feasible nexus between nutrition and non-genetic exposure (around the time of conception and in epigenetic changes) in the expression of major genes identified in renal organogenesis...
December 2016: Biomedical Reports
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