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https://www.readbyqxmd.com/read/28107481/bet-inhibitors-disrupt-rad21-dependent-conformational-control-of-kshv-latency
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28105268/great-therapeutic-potential-of-peptidylarginine-deiminase-4-pad4-inhibitors-treatment-of-rheumatoid-arthritis-epigenetic-tools-regulation-of-pluripotency-in-stem-cells-and-more
#14
EDITORIAL
https://www.readbyqxmd.com/read/28105243/detection-of-aberrant-methylated-sept9-and-ntrk3-genes-in-sporadic-colorectal-cancer-patients-as-a-potential-diagnostic-biomarker
#15
Shahin Behrouz Sharif, Shahriar Hashemzadeh, Reza Mousavi Ardehaie, Amirtaher Eftekharsadat, Mortaza Ghojazadeh, Amir Hossein Mehrtash, Mehrdad Asghari Estiar, Ladan Teimoori-Toolabi, Ebrahim Sakhinia
Colorectal cancer (CRC) is one of the most common malignancies, and the third leading cause of cancer mortality worldwide. Timely detection of CRC in patients with earlier stages provides the highest rate of survival. Epigenetic alterations are important in the occurrence and progression of CRC, and represent the primary modifications of cancer cells. Therefore, detection of these alterations in CRC cases are thought to hold great promise as diagnostic biomarkers. It has been shown that the SEPT9 and NTRK3 genes are aberrantly methylated and their detection can be used as biomarkers for early diagnosis of CRC...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104796/clonal-hematopoiesis-associated-with-tet2-deficiency-accelerates-atherosclerosis-development-in-mice
#16
José J Fuster, Susan MacLauchlan, María A Zuriaga, Maya N Polackal, Allison C Ostriker, Raja Chakraborty, Chia-Ling Wu, Soichi Sano, Sujatha Muralidharan, Cristina Rius, Jacqueline Vuong, Sophia Jacob, Varsha Muralidhar, Avril A B Robertson, Matthew A Cooper, Vicente Andrés, Karen K Hirschi, Kathleen A Martin, Kenneth Walsh
Human aging is associated with an increased frequency of somatic mutations in hematopoietic cells. Several of these recurrent mutations, including those in the gene encoding the epigenetic modifier enzyme TET2, promote expansion of the mutant blood cells. This "clonal hematopoiesis" correlates with an increased risk of atherosclerotic cardiovascular disease. Here we studied the effects of the expansion of Tet2-mutant cells in atherosclerosis-prone, low-density lipoprotein receptor-deficient (Ldlr-/-) mice. We found that partial bone marrow reconstitution with Tet2-deficient cells was sufficient for their clonal expansion and led to a marked increase in atherosclerotic plaque size...
January 19, 2017: Science
https://www.readbyqxmd.com/read/28104764/long-noncoding-rnas-in-pathological-cardiac-remodeling
#17
Janika Viereck, Thomas Thum
A novel long noncoding RNA Chaer acts as noncoding epigenetic regulator at the onset of cardiac hypertrophy and enables an improved understanding about the complex mechanisms in cardiovascular disease.
January 20, 2017: Circulation Research
https://www.readbyqxmd.com/read/28104380/-evolutionary-medicine-a-new-look-on-health-and-disease
#18
F Bauduer
Evolutionary medicine represents an innovative approach deriving from evolutionary biology. It includes the initial Darwin's view, its actualization in the light of progresses in genetics and also dissident theories (i.e. non gene-based) particularly epigenetics. This approach enables us to reconsider the pathophysiology of numerous diseases, as for instance, infection, and our so-called diseases of civilization especially obesity, type 2 diabetes, allergy or cancer. Evolutionary medicine may also improve our knowledge regarding inter-individual variation in susceptibility to disease or drugs...
January 16, 2017: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/28103888/photoreceptor-protection-via-blockade-of-bet-epigenetic-readers-in-a-murine-model-of-inherited-retinal-degeneration
#19
Lei Zhao, Jun Li, Yingmei Fu, Mengxue Zhang, Bowen Wang, Jonathan Ouellette, Pawan K Shahi, Bikash R Pattnaik, Jyoti J Watters, Wai T Wong, Lian-Wang Guo
BACKGROUND: The bromodomain and extraterminal domain (BET) family proteins (BET2, BET3, and BET4) "read" (bind) histone acetylation marks via two distinct bromodomains (Brom1 and Brom2) facilitating transcriptional activation. These epigenetic "readers" play crucial roles in pathogenic processes such as inflammation. The role of BETs in influencing the degenerative process in the retina is however unknown. METHODS: We employed the rd10 mouse model (Pde6b (rd10) mutation) of retinitis pigmentosa (RP) to examine the involvement of BET proteins in retinal neurodegeneration...
January 19, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28103887/microrna-expression-patterns-and-signalling-pathways-in-the-development-and-progression-of-childhood-solid-tumours
#20
REVIEW
Anna L Leichter, Michael J Sullivan, Michael R Eccles, Aniruddha Chatterjee
The development of childhood solid tumours is tied to early developmental processes. These tumours may be complex and heterogeneous, and elucidating the aberrant mechanisms that alter the early embryonic environment and lead to disease is essential to our understanding of how these tumours function. MicroRNAs (miRNAs) are vital regulators of gene expression at all stages of development, and their crosstalk via developmental signalling pathways is essential for orchestrating regulatory control in processes such as proliferation, differentiation and apoptosis of cells...
January 19, 2017: Molecular Cancer
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