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Epigenetic priming

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https://www.readbyqxmd.com/read/28286180/dysregulation-of-bet-proteins-in-levodopa-induced-dyskinesia
#1
David A Figge, David G Standaert
Levodopa (L-DOPA) remains the most effective pharmacological treatment for Parkinson Disease (PD) but its use is limited by the development of debilitating drug-related side effects, particularly L-DOPA induced dyskinesia (LID). LID is a consequence of long-term L-DOPA use, and in model systems is characterized by a "priming effect", whereby initial administrations of L-DOPA trigger a sensitized biochemical and transcriptional response upon subsequent dopaminergic stimulation. Preliminary studies into the mechanisms underlying this cellular memory have indicated an important role for epigenetic change but many of the downstream mechanisms remain unknown...
March 9, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28249902/hypercholesterolemia-increases-colorectal-cancer-incidence-by-reducing-production-of-nkt-and-%C3%AE-%C3%AE-t-cells-from-hematopoietic-stem-cells
#2
Guodong Tie, Jinglian Yan, Lyne Khair, Julia Messina, April Deng, Joonsoo Kang, Thomas Fazzio, Louis M Messina
Obesity will soon surpass smoking as the most preventable cause of cancer. Hypercholesterolemia, a common comorbidity of obesity, has been shown to increase cancer risk, especially colorectal cancer. However, the mechanism by which hypercholesterolemia or any metabolic disorder increases cancer risk remains unknown. In this study, we show that hypercholesterolemia increases the incidence and pathological severity of colorectal neoplasia in two independent mouse models. Hypochlosterolemia induced an oxidant-stress dependent increase in miR101c which downregulated Tet1 in hematopoietic stem cells (HSC), resulting in reduced expression of genes critical to natural killer T cell (NKT) and γδ T cell differentiation...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28229117/dna-methylation-data-for-identification-of-epigenetic-targets-of-resveratrol-in-triple-negative-breast-cancer-cells
#3
Rubiceli Medina-Aguilar, Carlos Pérez-Plasencia, Patricio Gariglio, Laurence A Marchat, Ali Flores-Pérez, César López-Camarillo, Jaime García Mena
Previous studies revealed that some bioactive food components have anti-cancer effects. However epigenetic effects of dietary compound resveratrol are largely unknown in breast cancer cells (M.A. Dawson, T. Kouzarides, 2012) [1]. Here we provide novel data and comparisons of DNA methylation status of promoter gene regions in response to resveratrol treatment at 24 h and 48 h versus untreated MDA-MB-231 breast cancer cells. DNA methylation changes were measured using Array-PRIMES method (aPRIMES) followed by whole-genome hybridization using human DNA methylation promoter microarray NimbleGen HG18 Refseq Promoter 3×720 K array...
April 2017: Data in Brief
https://www.readbyqxmd.com/read/28228641/evaluation-of-trained-immunity-by-%C3%AE-1-3-d-glucan-on-murine-monocytes-in-vitro-and-duration-of-response-in-vivo
#4
Pablo Garcia-Valtanen, Ruth Marian Guzman-Genuino, David L Williams, John D Hayball, Kerrilyn R Diener
The β-1, 3 (d)-glucan (β-glucan) present in the cell wall of Candida albicans induces epigenetic changes in human monocytes resulting in primed macrophages exhibiting increased cytokine responsiveness to reinfection. This phenomenon is referred to as trained immunity or innate immune memory. However, whether β-glucan can reprogramme murine monocytes in vitro or induce lasting effects in vivo has yet to be elucidated. Thus, purified murine spleen-derived monocytes were primed with β-glucan in vitro and assessed for markers of differentiation and survival...
March 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28226238/defense-priming-an-adaptive-part-of-induced-resistance
#5
Brigitte Mauch-Mani, Ivan Baccelli, Estrella Luna, Victor Flors
Priming is an adaptive strategy that improves the defensive capacity of plants. This phenomenon is marked by an enhanced activation of induced defense mechanisms. Stimuli from pathogens, beneficial microbes, or arthropods, as well as chemicals and abiotic cues, can trigger the establishment of priming by acting as warning signals. Upon stimulus perception, changes may occur in the plant at the physiological, transcriptional, metabolic, and epigenetic levels. This phase is called the priming phase. Upon subsequent challenge, the plant effectively mounts a faster and/or stronger defense response that defines the postchallenge primed state and results in increased resistance and/or stress tolerance...
February 2, 2017: Annual Review of Plant Biology
https://www.readbyqxmd.com/read/28192409/melanocyte-transformation-requires-complete-loss-of-all-pocket-protein-function-via-a-mechanism-that-mitigates-the-need-for-mapk-pathway-activation
#6
I D Tonks, P Mukhopadhyay, W A Schroder, A Sorolla, A W Mould, H Y Handoko, B Ferguson, H K Muller, P Keith, N K Hayward, G J Walker, G F Kay
Deregulation of p16INK4A is a critical event in melanoma susceptibility and progression. It is generally assumed that the major effect of loss of p16 function is mediated through the CDK-cyclin pathway via its influence on the pocket protein (PP) pRb. However, there are also two other PPs, p107 and p130, which, when phosphorylated by CDK-cyclin complexes, play a role in permitting cell progression. Cohorts of mice carrying melanocyte-specific knockouts (KOs) of various combinations of the three PPs were generated...
February 13, 2017: Oncogene
https://www.readbyqxmd.com/read/28185904/chromatin-priming-of-genes-in-development-concepts-mechanisms-and-consequences
#7
REVIEW
Constanze Bonifer, Peter N Cockerill
During ontogeny, cells progress through multiple alternate differentiation states by activating distinct gene regulatory networks. In this review, we highlight the important role of chromatin priming in facilitating gene activation during lineage specification and in maintaining an epigenetic memory of previous gene activation. We show that chromatin priming is part of a hugely diverse repertoire of regulatory mechanisms that genes use to ensure that they are expressed at the correct time, in the correct cell type, and at the correct level, but also that they react to signals...
February 7, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28174112/epigenetic-basis-of-the-dark-side-of-alcohol-addiction
#8
REVIEW
Subhash C Pandey, Evan J Kyzar, Huaibo Zhang
Alcoholism is a complex brain disease characterized by three distinct stages of the addiction cycle that manifest as neuroadaptive changes in the brain. One such stage of the addiction cycle is alcohol withdrawal and the negative affective states that promote drinking and maintain addiction. Repeated alcohol use, genetic predisposition to alcoholism and anxiety, and alcohol exposure during crucial developmental periods all contribute to the development of alcohol-induced withdrawal and negative affective symptoms...
February 4, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28173760/grandparental-immune-priming-in-the-pipefish-syngnathus-typhle
#9
Anne Beemelmanns, Olivia Roth
BACKGROUND: Phenotypic changes in response to environmental influences can persist from one generation into the next. In many systems parental parasite experience influences offspring immune responses, known as transgenerational immune priming (TGIP). TGIP in vertebrates is mainly maternal and short-term, supporting the adaptive immune system of the offspring during its maturation. However, if fathers and offspring have a close physical connection, evolution of additional paternal immune priming can be adaptive...
February 7, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28169291/hotspots-of-aberrant-enhancer-activity-punctuate-the-colorectal-cancer-epigenome
#10
Andrea J Cohen, Alina Saiakhova, Olivia Corradin, Jennifer M Luppino, Katreya Lovrenert, Cynthia F Bartels, James J Morrow, Stephen C Mack, Gursimran Dhillon, Lydia Beard, Lois Myeroff, Matthew F Kalady, Joseph Willis, James E Bradner, Ruth A Keri, Nathan A Berger, Shondra M Pruett-Miller, Sanford D Markowitz, Peter C Scacheri
In addition to mutations in genes, aberrant enhancer element activity at non-coding regions of the genome is a key driver of tumorigenesis. Here, we perform epigenomic enhancer profiling of a cohort of more than forty genetically diverse human colorectal cancer (CRC) specimens. Using normal colonic crypt epithelium as a comparator, we identify enhancers with recurrently gained or lost activity across CRC specimens. Of the enhancers highly recurrently activated in CRC, most are constituents of super enhancers, are occupied by AP-1 and cohesin complex members, and originate from primed chromatin...
February 7, 2017: Nature Communications
https://www.readbyqxmd.com/read/28157493/soil-primes-the-seed-epigenetic-landscape-drives-tumor-behavior
#11
Ramon J Whitson, Anthony E Oro
Whether invasive tumor phenotypes like EMT arise from oncogenic drivers or from priming of the pre-tumor cell of origin remains unknown. In this issue of Cell Stem Cell, Latil et al. (2017) show that the pre-tumor niche establishes a chromatin state predisposing squamous cell carcinomas to undergo EMT and metastasis, suggesting that the pre-tumor epigenome has prognostic value.
February 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28149332/the-immunomodulatory-anticancer-agent-rrx-001-induces-an-interferon-response-through-epigenetic-induction-of-viral-mimicry
#12
Hongjuan Zhao, Shoucheng Ning, Rosalie Nolley, Jan Scicinski, Bryan Oronsky, Susan J Knox, Donna M Peehl
BACKGROUND: RRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28143843/formative-pluripotency-the-executive-phase-in-a-developmental-continuum
#13
REVIEW
Austin Smith
The regulative capability of single cells to give rise to all primary embryonic lineages is termed pluripotency. Observations of fluctuating gene expression and phenotypic heterogeneity in vitro have fostered a conception of pluripotency as an intrinsically metastable and precarious state. However, in the embryo and in defined culture environments the properties of pluripotent cells change in an orderly sequence. Two phases of pluripotency, called naïve and primed, have previously been described. In this Hypothesis article, a third phase, called formative pluripotency, is proposed to exist as part of a developmental continuum between the naïve and primed phases...
February 1, 2017: Development
https://www.readbyqxmd.com/read/28128194/a-molecular-roadmap-for-induced-multi-lineage-trans-differentiation-of-fibroblasts-by-chemical-combinations
#14
Xiaoping Han, Hao Yu, Daosheng Huang, Yang Xu, Assieh Saadatpour, Xia Li, Lengmei Wang, Jie Yu, Luca Pinello, Shujing Lai, Mengmeng Jiang, Xueying Tian, Fen Zhang, Yanhong Cen, Yuko Fujiwara, Wei Zhu, Bin Zhou, Tianhua Zhou, Hongwei Ouyang, Jianan Wang, Guo-Cheng Yuan, Shumin Duan, Stuart H Orkin, Guoji Guo
Recent advances have demonstrated the power of small molecules in promoting cellular reprogramming. Yet, the full potential of such chemicals in cell fate manipulation and the underlying mechanisms require further characterization. Through functional screening assays, we find that mouse embryonic fibroblast cells can be induced to trans-differentiate into a wide range of somatic lineages simultaneously by treatment with a combination of four chemicals. Genomic analysis of the process indicates activation of multi-lineage modules and relaxation of epigenetic silencing programs...
March 2017: Cell Research
https://www.readbyqxmd.com/read/28111014/tethered-oligonucleotide-primed-sequencing-top-seq-a-high-resolution-economical-approach-for-dna-epigenome-profiling
#15
Zdislav Staševskij, Povilas Gibas, Juozas Gordevičius, Edita Kriukienė, Saulius Klimašauskas
Modification of CG dinucleotides in DNA is part of epigenetic regulation of gene function in vertebrates and is associated with complex human disease. Bisulfite sequencing permits high-resolution analysis of cytosine modification in mammalian genomes; however, its utility is often limited due to substantial cost. Here, we describe an alternative epigenome profiling approach, named TOP-seq, which is based on covalent tagging of individual unmodified CG sites followed by non-homologous priming of the DNA polymerase action at these sites to directly produce adjoining regions for their sequencing and precise genomic mapping...
February 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28105774/stiffness-controlled-thermoresponsive-hydrogels-for-cell-harvesting-with-sustained-mechanical-memory
#16
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/28089671/pdgfr%C3%AE-cells-in-embryonic-stem-cell-cultures-represent-the-in%C3%A2-vitro-equivalent-of-the-pre-implantation-primitive-endoderm-precursors
#17
Antonio Lo Nigro, Anchel de Jaime-Soguero, Rita Khoueiry, Dong Seong Cho, Giorgia Maria Ferlazzo, Ilaria Perini, Vanesa Abon Escalona, Xabier Lopez Aranguren, Susana M Chuva de Sousa Lopes, Kian Peng Koh, Pier Giulio Conaldi, Wei-Shou Hu, An Zwijsen, Frederic Lluis, Catherine M Verfaillie
In early mouse pre-implantation development, primitive endoderm (PrE) precursors are platelet-derived growth factor receptor alpha (PDGFRα) positive. Here, we demonstrated that cultured mouse embryonic stem cells (mESCs) express PDGFRα heterogeneously, fluctuating between a PDGFRα+ (PrE-primed) and a platelet endothelial cell adhesion molecule 1 (PECAM1)-positive state (epiblast-primed). The two surface markers can be co-detected on a third subpopulation, expressing epiblast and PrE determinants (double-positive)...
February 14, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28076901/nuclear-factor-one-transcription-factors-as-epigenetic-regulators-in-cancer
#18
REVIEW
Mitchell Fane, Lachlan Harris, Aaron G Smith, Michael Piper
Tumour heterogeneity poses a distinct obstacle to therapeutic intervention. While the initiation of tumours across various physiological systems is frequently associated with signature mutations in genes that drive proliferation and bypass senescence, increasing evidence suggests that tumour progression and clonal diversity is driven at an epigenetic level. The tumour microenvironment plays a key role in driving diversity as cells adapt to demands during tumour growth, and is thought to drive certain subpopulations back to a stem cell-like state...
January 11, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28065711/a-comparison-of-the-effects-of-male-pheromone-priming-and-optogenetic-inhibition-of-accessory-olfactory-bulb-forebrain-inputs-on-the-sexual-behavior-of-estrous-female-mice
#19
Elizabeth A McCarthy, Tenzin Kunkhyen, Wayne J Korzan, Ajay Naik, Arman Maqsudlu, James A Cherry, Michael J Baum
Previous research has shown that repeated testing with a stimulus male is required for ovariectomized, hormone-primed female mice to become sexually receptive (show maximal lordosis quotients; LQs) and that drug-induced, epigenetic enhancement of estradiol receptor function accelerated the improvement in LQs otherwise shown by estrous females with repeated testing. We asked whether pre-exposure to male pheromones ('pheromone priming') would also accelerate the improvement in LQs with repeated tests and whether optogenetic inhibition of accessory olfactory bulb (AOB) projection neurons could inhibit lordosis in sexually experienced estrous female mice...
March 2017: Hormones and Behavior
https://www.readbyqxmd.com/read/28064082/novel-flavonol-analogues-as-potential-inhibitors-of-jmjd3-histone-demethylase-a-study-based-on-molecular-modelling
#20
Sanchari Basu Mallik, Aravinda Pai, Rekha R Shenoy, B S Jayashree
Epigenetic modulation of gene expression has drawn enormous attention among researchers globally in the present scenario. Since their discovery, Jmj-C histone demethylases were identified as useful markers in understanding the role of epigenetics in inflammatory conditions and in cancer as well. This has created arousal of interest in search of suitable candidates. Potential inhibitors from various other scaffolds such as hydroxyquinolines, hydroxamic acids and triazolopyridines have already been identified and reported...
December 13, 2016: Journal of Molecular Graphics & Modelling
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