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Epigenetic priming

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https://www.readbyqxmd.com/read/28445481/hypomethylating-agents-synergize-with-irinotecan-to-improve-response-to-chemotherapy-in-colorectal-cancer-cells
#1
Anup Sharma, Rajita Vatapalli, Eihab Abdelfatah, K Wyatt McMahon, Zachary Kerner, Angela A Guzzetta, Jasvinder Singh, Cynthia Zahnow, Stephen B Baylin, Sashidhar Yerram, Yue Hu, Nilofer Azad, Nita Ahuja
Colorectal cancer (CRC) is the second leading cause of cancer death in the United States. In the metastatic setting, the majority of patients respond to initial therapies but eventually develop resistance and progress. In this study, we test the hypothesis that priming with epigenetic therapy sensitizes CRC cell lines, which were previously resistant to subsequent chemotherapeutic agents. When multiple CRC cell lines are first exposed to 500 nM of the DNA demethylating agent, 5-aza-cytidine (AZA) in-vitro, and the cells then established as in-vivo xenografts in untreated NOD-SCID mice; there is an enhanced response to cytotoxic chemotherapy with agents commonly used in CRC treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28400369/in-utero-particulate-matter-exposure-produces-heart-failure-electrical-remodeling-and-epigenetic-changes-at-adulthood
#2
Vineeta Tanwar, Matthew W Gorr, Markus Velten, Clayton M Eichenseer, Victor P Long, Ingrid M Bonilla, Vikram Shettigar, Mark T Ziolo, Jonathan P Davis, Stephen H Baine, Cynthia A Carnes, Loren E Wold
BACKGROUND: Particulate matter (PM; PM2.5 [PM with diameters of <2.5 μm]) exposure during development is strongly associated with adverse cardiovascular outcomes at adulthood. In the present study, we tested the hypothesis that in utero PM2.5 exposure alone could alter cardiac structure and function at adulthood. METHODS AND RESULTS: Female FVB mice were exposed either to filtered air or PM2.5 at an average concentration of 73.61 μg/m(3) for 6 h/day, 7 days/week throughout pregnancy...
April 11, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28396520/cytosine-modifications-modulate-the-chromatin-architecture-of-transcriptional-enhancers
#3
Elise A Mahé, Thierry Madigou, Aurélien A Sérandour, Maud Bizot, Stéphane Avner, Frédéric Chalmel, Gaëlle Palierne, Raphaël Métivier, Gilles Salbert
Epigenetic mechanisms are believed to play key roles in the establishment of cell-specific transcription programs. Accordingly, the modified bases 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) have been observed in DNA of genomic regulatory regions such as enhancers, and oxidation of 5mC into 5hmC by Ten Eleven Translocation (TET) proteins correlates with enhancer activation. However, the functional relationship between cytosine modifications and the chromatin architecture of enhancers remains elusive...
April 10, 2017: Genome Research
https://www.readbyqxmd.com/read/28359286/the-double-edged-sword-of-re-expression-of-genes-by-hypomethylating-agents-from-viral-mimicry-to-exploitation-as-priming-agents-for-targeted-immune-checkpoint-modulation
#4
REVIEW
Florian Wolff, Michael Leisch, Richard Greil, Angela Risch, Lisa Pleyer
Hypomethylating agents (HMAs) have been widely used over the last decade, approved for use in myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML) and acute myeloid leukemia (AML). The proposed central mechanism of action of HMAs, is the reversal of aberrant methylation in tumor cells, thus reactivating CpG-island promoters and leading to (re)expression of tumor suppressor genes. Recent investigations into the mode of action of azacitidine (AZA) and decitabine (DAC) have revealed new molecular mechanisms that impinge on tumor immunity via induction of an interferon response, through activation of endogenous retroviral elements (ERVs) that are normally epigenetically silenced...
March 31, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28352611/targeting-the-metabolic-reprogramming-that-controls-epithelial-to-mesenchymal-transition-in-aggressive-tumors
#5
REVIEW
Andrea Morandi, Maria Letizia Taddei, Paola Chiarugi, Elisa Giannoni
The epithelial-to-mesenchymal transition (EMT) process allows the trans-differentiation of a cell with epithelial features into a cell with mesenchymal characteristics. This process has been reported to be a key priming event for tumor development and therefore EMT activation is now considered an established trait of malignancy. The transcriptional and epigenetic reprogramming that governs EMT has been extensively characterized and reviewed in the last decade. However, increasing evidence demonstrates a correlation between metabolic reprogramming and EMT execution...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28286180/dysregulation-of-bet-proteins-in-levodopa-induced-dyskinesia
#6
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...
June 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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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