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Epigenetic priming

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https://www.readbyqxmd.com/read/28511092/epigenetics-and-immunotherapy-the-current-state-of-play
#1
REVIEW
Jennifer Dunn, Sudha Rao
Cancer cells employ a number of mechanisms to escape immunosurveillance and facilitate tumour progression. The recent explosion of interest in immunotherapy, especially immune checkpoint blockade, is a result of discoveries about the fundamental ligand-receptor interactions that occur between immune and cancer cells within the tumour microenvironment. Distinct ligands expressed by cancer cells engage with cell surface receptors on immune cells, triggering inhibitory pathways (such as PD-1/PD-L1) that render immune cells immunologically tolerant...
May 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28494866/epithelial-histone-deacetylase-3-instructs-intestinal-immunity-by-coordinating-local-lymphocyte-activation
#2
Nazanin Navabi, Jordan Whitt, Shu-En Wu, Vivienne Woo, Jessica Moncivaiz, Michael B Jordan, Bruce A Vallance, Sing Sing Way, Theresa Alenghat
Mucosal tissues are constantly in direct contact with diverse beneficial and pathogenic microbes, highlighting the need for orchestrating complex microbial signals to sustain effective host defense. Here, we show an essential role for intestinal epithelial cell expression of histone deacetylase 3 (HDAC3) in responding to pathogenic microbes and activating protective innate immunity. Mice lacking HDAC3 in intestinal epithelial cells were more susceptible to Citrobacter rodentium when under tonic stimulation by the commensal microbiota...
May 9, 2017: Cell Reports
https://www.readbyqxmd.com/read/28481620/ifn%C3%AE-influences-epithelial-anti-viral-responses-via-histone-methylation-of-the-rig-i-promoter
#3
C Mirella Spalluto, Akul Singhania, Doriana Cellura, Christopher H Woelk, Tilman Sanchez-Elsner, Karl J Staples, Tom M A Wilkinson
The asthmatic lung is prone to respiratory viral infections that exacerbate the symptoms of the underlying disease. Recent work has suggested that a deficient Th1 response in early life may lead to these aberrant anti-viral responses. We investigated whether the inflammatory environment of the airway epithelium could modulate anti-viral gene expression via epigenetic mechanisms, in order to study the development of a long-term dysregulation of innate responses, which are a hallmark of asthma. We primed AALEB, a human bronchial epithelial cell line, with IFNγ and IL13 and subsequently infected cells with Respiratory Syncytial Virus (RSV) and innate anti-viral genes expression and their epigenetic markers were analysed...
May 8, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28479992/pathogen-induced-maternal-effects-result-in-enhanced-immune-responsiveness-across-generations
#4
Rebeca B Rosengaus, Nicole Hays, Colette Biro, James Kemos, Muizz Zaman, Joseph Murray, Bruck Gezahegn, Wendy Smith
Parental investment theory postulates that adults can accurately perceive cues from their surroundings, anticipate the needs of future offspring based on those cues, and selectively allocate nongenetic resources to their progeny. Such context-dependent parental contributions can result in phenotypically variable offspring. Consistent with these predictions, we show that bacterially exposed Manduca sexta mothers oviposited significantly more variable embryos (as measured by mass, volume, hatching time, and hatching success) relative to naïve and control mothers...
May 2017: Ecology and Evolution
https://www.readbyqxmd.com/read/28475876/keep-them-close-prc2-poises-enhancer-promoter-interactions-at-anterior-neuronal-genes
#5
Giulia Caglio, Elena Torlai Triglia, Ana Pombo
Enhancers exist in different epigenetic states: active, primed, or poised. However, it is not yet understood how the different enhancer states influence gene activation. In this issue of Cell Stem Cell, Cruz-Molina et al. (2017) unravel how poised enhancers activate anterior neural genes and the role of Polycomb proteins in enhancer-promoter contacts.
May 4, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28465481/genome-wide-screening-of-dna-methylation-associated-with-lymph-node-metastasis-in-esophageal-squamous-cell-carcinoma
#6
Hiroaki Nagata, Ken-Ichi Kozaki, Tomoki Muramatsu, Hidekazu Hiramoto, Kousuke Tanimoto, Naoto Fujiwara, Seiya Imoto, Daisuke Ichikawa, Eigo Otsuji, Satoru Miyano, Tatsuyuki Kawano, Johji Inazawa
Lymph node metastasis (LNM) of esophageal squamous cell carcinoma (ESCC) is well-known to be an early event associated with poor prognosis in patients with ESCC. Recently, tumor-specific aberrant DNA methylation of CpG islands around the promoter regions of tumor-related genes has been investigated as a possible biomarker for use in early diagnosis and prediction of prognosis. However, there are few DNA methylation markers able to predict the presence of LNM in ESCC. To identify DNA methylation markers associated with LNM of ESCC, we performed a genome-wide screening of DNA methylation status in a discovery cohort of 67 primary ESCC tissues and their paired normal esophageal tissues using the Illumina Infinium HumanMethylation450 BeadChip...
April 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445481/hypomethylating-agents-synergize-with-irinotecan-to-improve-response-to-chemotherapy-in-colorectal-cancer-cells
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
Guodong Tie, Jinglian Yan, Lyne Khair, Julia A 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 pathologic severity of colorectal neoplasia in two independent mouse models. Hypocholesterolemia 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...
May 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
#14
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
#15
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
#16
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...
April 28, 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
#17
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
#18
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...
May 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28174112/epigenetic-basis-of-the-dark-side-of-alcohol-addiction
#19
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
#20
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
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