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Epigenetic priming

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https://www.readbyqxmd.com/read/29146205/pax3-foxo1-zooming-in-on-an-undruggable-target
#1
REVIEW
Marco Wachtel, Beat W Schäfer
Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets...
November 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29134247/epigenetic-differences-between-na%C3%A3-ve-and-primed-pluripotent-stem-cells
#2
REVIEW
Saori Takahashi, Shin Kobayashi, Ichiro Hiratani
It has been 8 years since the concept of naïve and primed pluripotent stem cell states was first proposed. Both are states of pluripotency, but exhibit slightly different properties. The naïve state represents the cellular state of the preimplantation mouse blastocyst inner cell mass, while the primed state is representative of the post-implantation epiblast cells. These two cell types exhibit clearly distinct developmental potential, as evidenced by the fact that naïve cells are able to contribute to blastocyst chimeras, while primed cells cannot...
November 13, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29133290/cd137-4-1bb-costimulation-modifies-dna-methylation-in-cd8-t-cell-relevant-genes
#3
M Angela Aznar, Sara Labiano, Angel Diaz-Lagares, Carmen Molina, Saray Garasa, Arantza Azpilicueta, Inaki Etxeberria, Alfonso R Sanchez-Paulete, Alan J Korman, Manel Esteller, Juan Sandoval, Ignacio Melero
CD137 (4-1BB) costimulation imprints long-term changes that instruct the ultimate behavior of T cells that have previously experienced CD137 ligation. Epigenetic changes could provide a suitable mechanism for these long-term consequences. Genome-wide DNA-methylation arrays were carried out on human peripheral blood CD8+ T lymphocytes stimulated with agonist monoclonal antibody to CD137, including urelumab, which is in phase I/II clinical trials for cancer immunotherapy. Several genes showed consistent methylation patterns in response to CD137 costimulation, which were confirmed by pyrosequencing in a series of healthy donors...
November 13, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/29128937/epigenetics-in-diabetic-nephropathy-immunity-and-metabolism
#4
REVIEW
Samuel T Keating, Janna A van Diepen, Niels P Riksen, Assam El-Osta
When it comes to the epigenome, there is a fine line between clarity and confusion-walk that line and you will discover another fascinating level of transcription control. With the genetic code representing the cornerstone of rules for information that is encoded to proteins somewhere above the genome level there is a set of rules by which chemical information is also read. These epigenetic modifications show a different side of the genetic code that is diverse and regulated, hence modifying genetic transcription transiently, ranging from short- to long-term alterations...
November 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/29123948/no-patient-left-behind-the-promise-of-immune-priming-with-epigenetic-agents
#5
REVIEW
Corey A Carter, Bryan T Oronsky, Joseph Roswarski, Arnold L Oronsky, Neil Oronsky, Jan Scicinski, Harry Lybeck, Michelle M Kim, Michelle Lybeck, Tony R Reid
Checkpoint inhibitors, monoclonal antibodies that inhibit PD-1 or CTLA-4, have revolutionized the treatment of multiple cancers. Despite the enthusiasm for the clinical successes of checkpoint inhibitors, and immunotherapy, in general, only a minority of patients with specific tumor types actually benefit from treatment. Emerging evidence implicates epigenetic alterations as a mechanism of clinical resistance to immunotherapy. This review presents evidence for that association, summarizes the epi-based mechanisms by which tumors evade immunogenic cell death, discusses epigenetic modulation as a component of an integrated strategy to boost anticancer T cell effector function in relation to a tumor immunosuppression cycle and, finally, makes the case that the success of this no-patient-left-behind strategy critically depends on the toxicity profile of the epigenetic agent(s)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29118980/sirt1-dependent-modulation-of-methylation-and-acetylation-of-histone-h3-on-lysine-9-h3k9-in-the-zygotic-pronuclei-improves-porcine-embryo-development
#6
Katerina Adamkova, Young-Joo Yi, Jaroslav Petr, Tereza Zalmanova, Kristyna Hoskova, Pavla Jelinkova, Jiri Moravec, Milena Kralickova, Miriam Sutovsky, Peter Sutovsky, Jan Nevoral
Background: The histone code is an established epigenetic regulator of early embryonic development in mammals. The lysine residue K9 of histone H3 (H3K9) is a prime target of SIRT1, a member of NAD(+)-dependent histone deacetylase family of enzymes targeting both histone and non-histone substrates. At present, little is known about SIRT1-modulation of H3K9 in zygotic pronuclei and its association with the success of preimplantation embryo development. Therefore, we evaluated the effect of SIRT1 activity on H3K9 methylation and acetylation in porcine zygotes and the significance of H3K9 modifications for early embryonic development...
2017: Journal of Animal Science and Biotechnology
https://www.readbyqxmd.com/read/29113750/epigenetic-regulation-of-astrocyte-function-in-neuroinflammation-and-neurodegeneration
#7
REVIEW
Matthew Neal, Jason R Richardson
Epigenetic mechanisms control various functions throughout the body, from cell fate determination in development to immune responses and inflammation. Neuroinflammation is one of the prime contributors to the initiation and progression of neurodegeneration in a variety of diseases, including Alzheimer's and Parkinson's diseases. Because astrocytes are the largest population of glial cells, they represent an important regulator of CNS function, both in health and disease. Only recently have studies begun to identify the epigenetic mechanisms regulating astrocyte responses in neurodegenerative diseases...
November 4, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29113308/kdm4a-as-a-prognostic-marker-of-oral-squamous-cell-carcinoma-evidence-from-tissue-microarray-studies-in-a-multicenter-cohort
#8
Xin Jin, Hao Xu, Xingyu Wu, Taiwen Li, Jing Li, Yu Zhou, Hongxia Dan, Lu Jiang, Xin Zeng, Ping Ji, Qianming Chen
Purpose: Previous studies have identified histone demethylase KDM4A to be a key epigenetic priming factor for the invasive squamous cell carcinoma growth and metastasis. The purpose of this study was to examine KDM4A as an independent prognostic marker in oral squamous cell carcinoma, using multicenter tissue microarrays. Results: The expression of KDM4A was significantly correlated with lymph node metastasis and TNM stage. KDM4A overexpression was associated with poor overall survival, and it was found to be a statistically significant independent predictor of all-cause mortality...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29082293/reprogram-murine-epiblast-stem-cells-by-epigenetic-inhibitors
#9
Hui Zhang, Yali Dou
Pluripotent stem cells in the naïve state are highly useful in regenerative medicine and tissue engineering. A robust reprogramming of the primed murine Epiblast Stem Cells (EpiSCs) to naïve pluripotency is feasible via chemical-only approach. This protocol described a method to reprogram murine EpiSCs by MM-401 treatment, which blocks histone H3K4 methylation by MLL1/KMT2A.
March 5, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29036928/plasma-mir-155-mir-203-and-mir-205-are-biomarkers-for-monitoring-of-primary-cutaneous-t-cell-lymphomas
#10
Nina Dusílková, Petra Bašová, Jindřich Polívka, Ondřej Kodet, Vojtěch Kulvait, Michal Pešta, Marek Trněný, Tomáš Stopka
Primary cutaneous T-cell lymphomas (CTCL) affect the skin and tend to transform and spread. CTCL involves primarily the Mycosis fungoides (MF) and more aggressive Sezary syndrome (SS). Oncogenic microRNAs (miRs) are stable epigenetic inhibitors often deregulated in the tumour and detectable as biomarkers in non-cellular fractions of peripheral blood. The tumour-specific expression of miR-155, miR-203, and miR-205 was shown to correctly diagnose CTCL. We herein asked whether these microRNAs can be used as plasma biomarkers for clinical CTCL monitoring...
October 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29034009/a-multicenter-randomized-study-of-decitabine-as-epigenetic-priming-with-induction-chemotherapy-in-children-with-aml
#11
Lia Gore, Timothy J Triche, Jason E Farrar, Daniel Wai, Christophe Legendre, Gerald C Gooden, Winnie S Liang, John Carpten, David Lee, Frank Alvaro, Margaret E Macy, Carola Arndt, Philip Barnette, Todd Cooper, Laura Martin, Aru Narendran, Jessica Pollard, Soheil Meshinchi, Jessica Boklan, Robert J Arceci, Bodour Salhia
BACKGROUND: Decitabine is a deoxycytidine nucleoside derivative inhibitor of DNA-methyltransferases, which has been studied extensively and is approved for myelodysplastic syndrome in adults but with less focus in children. Accordingly, we conducted a phase 1 multicenter, randomized, open-label study to evaluate decitabine pre-treatment before standard induction therapy in children with newly diagnosed AML to assess safety and tolerability and explore a number of biologic endpoints. RESULTS: Twenty-four patients were fully assessable for all study objectives per protocol (10 in Arm A = epigenetic priming induction, 14 in Arm B = standard induction)...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29032424/not-just-gene-expression-3d-implications-of-chromatin-modifications-during-sexual-plant-reproduction
#12
Stefanie Dukowic-Schulze, Chang Liu, Changbin Chen
DNA methylation and histone modifications are epigenetic changes on a DNA molecule that alter the three-dimensional (3D) structure locally as well as globally, impacting chromatin looping and packaging on a larger scale. Epigenetic marks thus inform higher-order chromosome organization and placement in the nucleus. Conventional epigenetic marks are joined by chromatin modifiers like cohesins, condensins and membrane-anchoring complexes to support particularly 3D chromosome organization. The most popular consequences of epigenetic modifications are gene expression changes, but chromatin modifications have implications beyond this, particularly in actively dividing cells and during sexual reproduction...
October 14, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/29024663/role-of-the-astroglial-glutamate-exchanger-xct-in-ventral-hippocampus-in-resilience-to-stress
#13
Carla Nasca, Benedetta Bigio, Danielle Zelli, Paolo de Angelis, Timothy Lau, Masahiro Okamoto, Hideyo Soya, Jason Ni, Lars Brichta, Paul Greengard, Rachael L Neve, Francis S Lee, Bruce S McEwen
We demonstrate that stress differentially regulates glutamate homeostasis in the dorsal and ventral hippocampus and identify a role for the astroglial xCT in ventral dentate gyrus (vDG) in stress and antidepressant responses. We provide an RNA-seq roadmap for the stress-sensitive vDG. The transcription factor REST binds to xCT promoter in co-occupancy with the epigenetic marker H3K27ac to regulate expression of xCT, which is also reduced in a genetic mouse model of inherent susceptibility to depressive-like behavior...
October 11, 2017: Neuron
https://www.readbyqxmd.com/read/28951953/plant-small-rnas-the-essential-epigenetic-regulators-of-gene-expression-for-salt-stress-responses-and-tolerance
#14
REVIEW
Vinay Kumar, Tushar Khare, Varsha Shriram, Shabir H Wani
Saline environment cues distort the plant growth, development and crop yield. Epigenetics has emerged as one of the prime themes in plant functional genomics for molecular-stress-physiology research, as copious studies have provided new visions into the epigenetic control of stress adaptations. The epigenetic control is associated with the regulation of the expression of stress-related genes which also comprises many steady alterations inherited in next cellular generation as stress memory. These epigenetic amendments also implicate induction of small RNA (sRNA)-mediated fine-tuning of transcriptional and post-transcriptional regulations of gene expression...
September 26, 2017: Plant Cell Reports
https://www.readbyqxmd.com/read/28951121/can-t-remember-to-forget-you-chromatin-based-priming-of-somatic-stress-responses
#15
REVIEW
Isabel Bäurle
In nature plants are exposed to frequent changes in their abiotic and biotic environment. While some environmental cues are used to gauge the environment and align growth and development, others are beyond the regularly encountered spectrum of a species and trigger stress responses. Such stressful conditions provide a potential threat to survival and integrity. Plants adapt to extreme environmental conditions through physiological adaptations that are usually transient and are maintained until stressful environments subside...
September 22, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28947657/human-x-chromosome-inactivation-and-reactivation-implications-for-cell-reprogramming-and-disease
#16
REVIEW
Irene Cantone, Amanda G Fisher
X-chromosome inactivation (XCI) is an exemplar of epigenetic regulation that is set up as pluripotent cells differentiate. Once established, XCI is stably propagated, but can be reversed in vivo or by pluripotent reprogramming in vitro Although reprogramming provides a useful model for inactive X (Xi) reactivation in mouse, the relative instability and heterogeneity of human embryonic stem (ES) cells and induced pluripotent stem cells hampers comparable progress in human. Here we review studies aimed at reactivating the human Xi using different reprogramming strategies...
November 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28939884/prc2-specifies-ectoderm-lineages-and-maintains-pluripotency-in-primed-but-not-na%C3%A3-ve-escs
#17
Yongli Shan, Zechuan Liang, Qi Xing, Tian Zhang, Bo Wang, Shulan Tian, Wenhao Huang, Yanqi Zhang, Jiao Yao, Yanling Zhu, Ke Huang, Yujian Liu, Xiaoshan Wang, Qianyu Chen, Jian Zhang, Bizhi Shang, Shengbiao Li, Xi Shi, Baojian Liao, Cong Zhang, Keyu Lai, Xiaofen Zhong, Xiaodong Shu, Jinyong Wang, Hongjie Yao, Jiekai Chen, Duanqing Pei, Guangjin Pan
Polycomb repressive complex 2 and the epigenetic mark that it deposits, H3K27me3, are evolutionarily conserved and play critical roles in development and cancer. However, their roles in cell fate decisions in early embryonic development remain poorly understood. Here we report that knockout of polycomb repressive complex 2 genes in human embryonic stem cells causes pluripotency loss and spontaneous differentiation toward a meso-endoderm fate, owing to de-repression of BMP signalling. Moreover, human embryonic stem cells with deletion of EZH1 or EZH2 fail to differentiate into ectoderm lineages...
September 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28898697/chronic-cigarette-smoke-induced-epigenomic-changes-precede-sensitization-of-bronchial-epithelial-cells-to-single-step-transformation-by-kras-mutations
#18
Michelle Vaz, Stephen Y Hwang, Ioannis Kagiampakis, Jillian Phallen, Ashwini Patil, Heather M O'Hagan, Lauren Murphy, Cynthia A Zahnow, Edward Gabrielson, Victor E Velculescu, Hariharan P Easwaran, Stephen B Baylin
We define how chronic cigarette smoke-induced time-dependent epigenetic alterations can sensitize human bronchial epithelial cells for transformation by a single oncogene. The smoke-induced chromatin changes include initial repressive polycomb marking of genes, later manifesting abnormal DNA methylation by 10 months. At this time, cells exhibit epithelial-to-mesenchymal changes, anchorage-independent growth, and upregulated RAS/MAPK signaling with silencing of hypermethylated genes, which normally inhibit these pathways and are associated with smoking-related non-small cell lung cancer...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898692/smoke-induced-changes-to-the-epigenome-provide-fertile-ground-for-oncogenic-mutation
#19
COMMENT
Susan J Clark, Peter L Molloy
How genetic and epigenetic events synergize to generate the oncogenic state is not well understood. In this issue of Cancer Cell, Vaz et al. provide compelling evidence that exposure to chronic cigarette smoke causes progressive epigenetic alterations that prime for key genetic events to drive the development of lung cancer.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28889080/reprogramming-of-rabbit-induced-pluripotent-stem-cells-toward-epiblast-and-chimeric-competency-using-kr%C3%A3-ppel-like-factors
#20
Yann Tapponnier, Marielle Afanassieff, Irène Aksoy, Maxime Aubry, Anaïs Moulin, Lucas Medjani, Wilhelm Bouchereau, Chloé Mayère, Pierre Osteil, Jazmine Nurse-Francis, Ioannis Oikonomakos, Thierry Joly, Luc Jouneau, Catherine Archilla, Barbara Schmaltz-Panneau, Nathalie Peynot, Harmonie Barasc, Alain Pinton, Jérome Lecardonnel, Elen Gocza, Nathalie Beaujean, Véronique Duranthon, Pierre Savatier
Rabbit induced pluripotent stem cells (rbiPSCs) possess the characteristic features of primed pluripotency as defined in rodents and primates. In the present study, we reprogrammed rbiPSCs using human Krüppel-like factors (KLFs) 2 and 4 and cultured them in a medium supplemented with fetal calf serum and leukemia inhibitory factor. These cells (designated rbEKA) were propagated by enzymatic dissociation for at least 30 passages, during which they maintained a normal karyotype. This new culturing protocol resulted in transcriptional and epigenetic reconfiguration, as substantiated by the expression of transcription factors and the presence of histone modifications associated with naïve pluripotency...
September 5, 2017: Stem Cell Research
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