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https://www.readbyqxmd.com/read/28440770/epigenetic-modulators-of-thyroid-cancer
#1
Sandra Rodríguez-Rodero, Elías Delgado-Álvarez, Lucía Díaz-Naya, Alicia Martín Nieto, Edelmiro Menéndez Torre
There are some well known factors involved in the etiology of thyroid cancer, including iodine deficiency, radiation exposure at early ages, or some genetic changes. However, epigenetic modulators that may contribute to development of these tumors and be helpful to for both their diagnosis and treatment have recently been discovered. The currently known changes in DNA methylation, histone modifications, and non-coding RNAs in each type of thyroid carcinoma are reviewed here.
January 2017: Endocrinol Diabetes Nutr
https://www.readbyqxmd.com/read/28438611/low-dietary-cholesterol-availability-during-lactation-programs-intestinal-absorption-of-cholesterol-in-adult-mice
#2
Lidiya G Dimova, Jan Freark de Boer, Josee Plantinga, Torsten Plösch, Menno Hoekstra, Henkjan J Verkade, Uwe J F Tietge
In nematodes, the intestine senses and integrates early-life dietary cues that lead to lifelong epigenetic adaptations to a perceived nutritional environment-it is not clear whether this process occurs in mammals. We aimed to establish a mouse model of reduced dietary cholesterol availability from maternal milk and investigate the consequences of decreased milk cholesterol availability, early in life, on metabolism of cholesterol in adult mice. We blocked intestinal absorption of cholesterol in milk fed to newborn mice by supplementing the food of dams (for 3 weeks between birth and weaning) with ezetimibe, which is secreted into milk...
April 21, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28421257/histone-deacetylase-inhibitors-reverse-age-related-increases-in-side-effects-of-haloperidol-in-mice
#3
Janitza L Montalvo-Ortiz, Daniel W Fisher, Guadalupe Rodríguez, Deyu Fang, John G Csernansky, Hongxin Dong
BACKGROUND: Older patients can be especially susceptible to antipsychotic-induced side effects, and the pharmacodynamic mechanism underlying this phenomenon remains unclear. We hypothesized that age-related epigenetic alterations lead to decreased expression and functionality of the dopamine D2 receptor (D2R), contributing to this susceptibility. METHODS: In this study, we treated young (2-3 months old) and aged (22-24 months old) C57BL/6 mice with the D2R antagonist haloperidol (HAL) once a day for 14 days to evaluate HAL-induced motor side effects...
April 18, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28393704/epigenetic-regulation-of-memory-therapeutic-potential-for-disorders
#4
Padmanabh Singh, Sweta Srivas, M K Thakur
Memory is a vital function which declines in different physiological and pathological conditions such as aging and neurodegenerative diseases. Research in the past has reported that memory formation and consolidation require the precise expression of synaptic plasticity genes. However, little is known about the regulation of these genes. Epigenetic modification is now a well established mechanism that regulates synaptic plasticity genes and neuronal functions including memory. Such modification includes mainly DNA methylation and hydroxymethylation, histone acetylation and methylation which involve chromatin modifying enzymes...
April 4, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28374742/the-histone-methyltransferase-ash1l-is-required-for-epidermal-homeostasis-in-mice
#5
Gang Li, Zhisheng Ye, Cheng Shi, Ling Sun, Min Han, Yuan Zhuang, Tian Xu, Shimin Zhao, Xiaohui Wu
Epidermal homeostasis under normal and healing conditions are critical for the physical and functional maintenance of the skin barrier. It requires a proper balance between keratinocyte proliferation and differentiation under genetic and epigenetic regulations. Here we show that mice carrying a hypomorphic mutation of the histone methyltransferase Ash1l [(absent, small, or homeotic)-like (Drosophila)] develop epidermal hyperplasia and impaired epidermal stratification upon aging. In adult mutants, loss of Ash1l leads to more proliferative keratinocytes in disturbed differentiation stages...
April 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28364391/histone-deacetylase-2-inhibition-attenuates-downregulation-of-hippocampal-plasticity-gene-expression-during-aging
#6
Padmanabh Singh, M K Thakur
The brain undergoes several anatomical, biochemical, and molecular changes during aging, which subsequently result in downregulation of synaptic plasticity genes and decline of memory. However, the regulation of these genes during aging is not clearly understood. Previously, we reported that the expression of histone deacetylase (HDAC)2 was upregulated in the hippocampus of old mice and negatively correlated with the decline in recognition memory. As HDAC2 regulates key synaptic plasticity neuronal immediate early genes (IEGs), we have examined their expression and epigenetic regulation...
March 31, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28361099/a-de-novo-splice-site-mutation-in-ehmt1-resulting-in-kleefstra-syndrome-with-pharmacogenomics-screening-and-behavior-therapy-for-regressive-behaviors
#7
Amit Kumar Mitra, Jessica Dodge, Jody Van Ness, Israel Sokeye, Brian Van Ness
BACKGROUND: Kleefstra syndrome (KS) is a rare autosomal dominant developmental disability, caused by microdeletions or intragenic mutations within the epigenetic regulator gene EHMT1 (euchromatic histone lysine N-methyltransferase 1). In addition to common features of autism, young adult regressive behaviors have been reported. However, the genetic downstream effects of the reported deletions or mutations on KS phenotype have not yet been completely explored. While genetic backgrounds affecting drug metabolism can have a profound effect on therapeutic interventions, pharmacogenomic variations are seldom considered in directing psychotropic therapies...
March 2017: Molecular Genetics & Genomic Medicine
https://www.readbyqxmd.com/read/28351383/diverse-interventions-that-extend-mouse-lifespan-suppress-shared-age-associated-epigenetic-changes-at-critical-gene-regulatory-regions
#8
John J Cole, Neil A Robertson, Mohammed Iqbal Rather, John P Thomson, Tony McBryan, Duncan Sproul, Tina Wang, Claire Brock, William Clark, Trey Ideker, Richard R Meehan, Richard A Miller, Holly M Brown-Borg, Peter D Adams
BACKGROUND: Age-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging "clock", a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 (df/df) mutation, calorie restriction and rapamycin...
March 28, 2017: Genome Biology
https://www.readbyqxmd.com/read/28347254/epigenetic-perturbation-driving-asleep-telomerase-reverse-transcriptase-possible-therapeutic-avenues-in-carcinoma
#9
REVIEW
Ajay Kumar, Pritish Nilednu, Azad Kumar, Nilesh Kumar Sharma
In the last decade, implications of human telomerase reverse transcriptase (hTERT), a component of ribonucleoprotein telomerase in aging, senescence, and stem cell are highly evident. Besides, the activation of hTERT is also being documented several cancer types including carcinoma. The awakening of telomerase during carcinoma initiation and development is being seen with different perspectives including genetic and epigenetic tools and events. In view of several tumor progenitors genes (also referred as epigenetic mediators), telomerase is placed as key enzyme to achieve the carcinoma phenotype and sustain during the progression...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28289478/cerebral-white-matter-hyperintensities-on-mri-and-acceleration-of-epigenetic-aging-the-atherosclerosis-risk-in-communities-study
#10
Abhay Raina, Xiaoping Zhao, Megan L Grove, Jan Bressler, Rebecca F Gottesman, Weihua Guan, James S Pankow, Eric Boerwinkle, Thomas H Mosley, Myriam Fornage
BACKGROUND: Cerebral white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) are part of the spectrum of brain vascular injury accompanying aging and are associated with a substantial risk of stroke and dementia. We investigated the association of cerebral WMH burden on MRI with a DNA methylation-based biomarker of aging, termed DNA methylation age acceleration, which represents the deviation of the DNA methylation-predicted age from the chronologic age. RESULTS: In this cross-sectional observational study of 713 African-American participants of the Atherosclerosis Risk in Communities study, aged 51-73 years, estimates of predicted age were obtained based on two algorithms (Hannum et al...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28284043/the-histone-variant-h3-3-claims-its-place-in-the-crowded-scene-of-epigenetics
#11
Daniele Bano, Antonia Piazzesi, Paolo Salomoni, Pierluigi Nicotera
Histones are evolutionarily conserved DNA-binding proteins. As scaffolding molecules, they significantly regulate the DNA packaging into the nucleus of all eukaryotic cells. As docking units, they influence the recruitment of the transcriptional machinery, thus establishing unique gene expression patterns that ultimately promote different biological outcomes. While canonical histones H3.1 and H3.2 are synthetized and loaded during DNA replication, the histone variant H3.3 is expressed and deposited into the chromatin throughout the cell cycle...
March 10, 2017: Aging
https://www.readbyqxmd.com/read/28283560/hdac7-ubiquitination-by-the-e3-ligase-cbx4-is-involved-in-contextual-fear-conditioning-memory-formation
#12
Xu Jing, Wen-Hai Sui, Shuai Wang, Xu-Feng Xu, Rong-Rong Yuan, Xiao-Rong Chen, Hui-Xian Ma, Ying-Xiao Zhu, Jin-Kai Sun, Fan Yi, Zhe-Yu Chen, Yue Wang
Histone acetylation, which comprises an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that HDAC inhibitors may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus (DH) of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4 h∼24 h), which was involved in long-term CFC memory formation...
March 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28188812/epigenetics-in-cancer-fundamentals-and-beyond
#13
REVIEW
Subhankar Biswas, C Mallikarjuna Rao
Activation of oncogenes or the deactivation of tumor suppressor genes has long been established as the fundamental mechanism leading towards carcinogenesis. Although this age old axiom is vastly accurate, thorough study over the last 15years has given us unprecedented information on the involvement of epigenetic in cancer. Various biochemical pathways that are essential towards tumorigenesis are regulated by the epigenetic phenomenons like remodeling of nucleosome by histone modifications, DNA methylation and miRNA mediated targeting of various genes...
February 8, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28176655/epigenetics-in-clinical-management-of-children-and-adolescents-with-brain-tumors
#14
Andres Morales La Madrid, Mark W Kieran
Central nervous system (CNS) tumors represent the second most prevalent group of cancers in children and adolescents, yet account for the majority of childhood cancer-related deaths and considerable morbidity among survivors, due to high-intensity non-selective standard therapies delivered to immature nervous system structures undergoing development. These tumors arise at different ages -not infrequently very early in life-, in different locations and cellular contexts, have varied cell types of origin, and have heterogeneous responses to the "classic" current therapeutic approaches...
February 3, 2017: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/28158904/effect-of-stress-on-human-biology-epigenetics-adaptation-inheritance-and-social-significance
#15
REVIEW
David T Denhardt
I present a brief introduction to epigenetics, focused primarily on methylation of the genome and various regulatory RNAs, modifications of associated histones, and their importance in enabling us to adapt to real and changing environmental, developmental, and social circumstances. Following this is a more extensive overview of how it impacts our inheritance, our entire life (which changes as we age), and how we interact with others. Throughout, I emphasize the critical influence that stress, of many varieties exerts, via epigenetic means, on much of how we live and survive, mostly in the brain...
February 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28123935/deletion-of-histone-deacetylase-3-in-adult-beta-cells-improves-glucose-tolerance-via-increased-insulin-secretion
#16
Jarrett R Remsberg, Benjamin N Ediger, Wesley Y Ho, Manashree Damle, Zhenghui Li, Christopher Teng, Cristina Lanzillotta, Doris A Stoffers, Mitchell A Lazar
OBJECTIVE: Histone deacetylases are epigenetic regulators known to control gene transcription in various tissues. A member of this family, histone deacetylase 3 (HDAC3), has been shown to regulate metabolic genes. Cell culture studies with HDAC-specific inhibitors and siRNA suggest that HDAC3 plays a role in pancreatic β-cell function, but a recent genetic study in mice has been contradictory. Here we address the functional role of HDAC3 in β-cells of adult mice. METHODS: An HDAC3 β-cell specific knockout was generated in adult MIP-CreERT transgenic mice using the Cre-loxP system...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28120717/understanding-epigenetic-alterations-in-alzheimer-s-and-parkinson-s-disease-towards-targeted-biomarkers-and-therapies
#17
Filippo Ciceri, David Rotllant, Tamara Maes
BACKGROUND: Alzheimer's and Parkinson's disease represent the two most common neurodegenerative disorders, affecting an increasing number of patients worldwide. Population ageing and lack of effective therapies and biomarkers strongly contribute to the socio-economical impact of these conditions. MESSAGE AND CONCLUSION: The aim of the review is to present a summary of the discoveries made on the epigenetics of Alzheimer's and Parkinson's disease, with a special focus on the recent advances towards the identification of new targeted therapies and biomarkers...
January 24, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28109165/melatonin-and-sirtuins-a-not-so-unexpected-relationship
#18
REVIEW
Juan C Mayo, Rosa M Sainz, Pedro González Menéndez, Vanesa Cepas, Dun-Xian Tan, Russel J Reiter
Epigenetic modifications, including methylation or acetylation as well as post-transcriptional modifications, are mechanisms used by eukaryotic cells to increase the genome diversity in terms of differential gene expression and protein diversity. Among these modifying enzymes, sirtuins, a class III histone deacetylase (HDAC) enzymes, are of particular importance. Sirtuins regulate the cell cycle, DNA repair, cell survival, and apoptosis, thus having important roles in normal and cancer cells. Sirtuins can also regulate metabolic pathways by changing preference for glycolysis under aerobic conditions as well as glutaminolysis...
January 21, 2017: Journal of Pineal Research
https://www.readbyqxmd.com/read/28108335/tryptase-catalyzed-core-histone-truncation-a%C3%A2-novel-epigenetic-regulatory-mechanism-in-mast-cells
#19
Fabio R Melo, Ola Wallerman, Aida Paivandy, Gabriela Calounova, Ann-Marie Gustafson, Benjamin R Sabari, Giuliano Zabucchi, C David Allis, Gunnar Pejler
BACKGROUND: Mast cells are key effector cells in allergic reactions. When activated to degranulate, they release a plethora of bioactive compounds from their secretory granules, including mast cell-restricted proteases such as tryptase. In a previous study, we showed that tryptase, in addition to its intragranular location, can be found within the nuclei of mast cells where it truncates core histones at their N-terminal ends. OBJECTIVE: Considering that the N-terminal portions of the core histones constitute sites for posttranslational modifications of major epigenetic impact, we evaluated whether histone truncation by tryptase could have an impact on epigenetic events in mast cells...
January 17, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28103888/photoreceptor-protection-via-blockade-of-bet-epigenetic-readers-in-a-murine-model-of-inherited-retinal-degeneration
#20
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
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