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Chromatin modulation

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https://www.readbyqxmd.com/read/28818332/antimicrobial-activity-and-acetylcholinesterase-inhibition-by-extracts-from-chromatin-modulated-fungi
#1
Matheus Thomaz Nogueira Silva Lima, Larissa Batista Dos Santos, Rafael Wesley Bastos, Jacques Robert Nicoli, Jacqueline Aparecida Takahashi
Major health challenges as the increasing number of cases of infections by antibiotic multiresistant microorganisms and cases of Alzheimer's disease have led to searching new control drugs. The present study aims to verify a new way of obtaining bioactive extracts from filamentous fungi with potential antimicrobial and acetylcholinesterase inhibitory activities, using epigenetic modulation to promote the expression of genes commonly silenced. For such finality, five filamentous fungal species (Talaromyces funiculosus, Talaromyces islandicus, Talaromyces minioluteus, Talaromyces pinophilus, Penicillium janthinellum) were grown or not with DNA methyltransferases inhibitors (procainamide or hydralazine) and/or a histone deacetylase inhibitor (suberohydroxamic acid)...
August 1, 2017: Brazilian Journal of Microbiology: [publication of the Brazilian Society for Microbiology]
https://www.readbyqxmd.com/read/28815539/long-noncoding-rnas-in-plants
#2
Hsiao-Lin V Wang, Julia A Chekanova
The eukaryotic genomes are pervasively transcribed. In addition to protein-coding RNAs, thousands of long noncoding RNAs (lncRNAs) modulate key molecular and biological processes. Most lncRNAs are found in the nucleus and associate with chromatin, but lncRNAs can function in both nuclear and cytoplasmic compartments. Emerging work has found that many lncRNAs regulate gene expression and can affect genome stability and nuclear domain organization both in plant and in the animal kingdom. Here, we describe the major plant lncRNAs and how they act, with a focus on research in Arabidopsis thaliana and our emerging understanding of lncRNA functions in serving as molecular sponges and decoys, functioning in regulation of transcription and silencing, particularly in RNA-directed DNA methylation, and in epigenetic regulation of flowering time...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28814742/the-candida-albicans-hir-histone-chaperone-regulates-the-yeast-to-hyphae-transition-by-controlling-the-sensitivity-to-morphogenesis-signals
#3
Sabrina Jenull, Michael Tscherner, Megha Gulati, Clarissa J Nobile, Neeraj Chauhan, Karl Kuchler
Morphological plasticity such as the yeast-to-hyphae transition is a key virulence factor of the human fungal pathogen Candida albicans. Hyphal formation is controlled by a multilayer regulatory network composed of environmental sensing, signaling, transcriptional modulators as well as chromatin modifications. Here, we demonstrate a novel role for the replication-independent HIR histone chaperone complex in fungal morphogenesis. HIR operates as a crucial modulator of hyphal development, since genetic ablation of the HIR complex subunit Hir1 decreases sensitivity to morphogenetic stimuli...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28813672/chromatin-and-transcriptional-analysis-of-mesoderm-progenitor-cells-identifies-hopx-as-a-regulator-of-primitive-hematopoiesis
#4
Nathan J Palpant, Yuliang Wang, Brandon Hadland, Rebecca J Zaunbrecher, Meredith Redd, Daniel Jones, Lil Pabon, Rajan Jain, Jonathan Epstein, Walter L Ruzzo, Ying Zheng, Irwin Bernstein, Adam Margolin, Charles E Murry
We analyzed chromatin dynamics and transcriptional activity of human embryonic stem cell (hESC)-derived cardiac progenitor cells (CPCs) and KDR(+)/CD34(+) endothelial cells generated from different mesodermal origins. Using an unbiased algorithm to hierarchically rank genes modulated at the level of chromatin and transcription, we identified candidate regulators of mesodermal lineage determination. HOPX, a non-DNA-binding homeodomain protein, was identified as a candidate regulator of blood-forming endothelial cells...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#5
Sebastiano Battaglia, Ellen Karasik, Bryan Gillard, Jennifer Williams, Trisha Winchester, Michael T Moser, Dominic J Smiraglia, Barbara A Foster
BACKGROUND: Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH)2-D3 (vitamin D) action in prostate cancer (PCa). METHODS: Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28811345/inhibitors-of-the-histone-methyltransferases-ezh2-1-induce-a-potent-antiviral-state-and-suppress-infection-by-diverse-viral-pathogens
#6
Jesse H Arbuckle, Paul J Gardina, David N Gordon, Heather D Hickman, Jonathan W Yewdell, Theodore C Pierson, Timothy G Myers, Thomas M Kristie
Epigenetic regulation is based on a network of complexes that modulate the chromatin character and structure of the genome to impact gene expression, cell fate, and development. Thus, epigenetic modulators represent novel therapeutic targets used to treat a range of diseases, including malignancies. Infectious pathogens such as herpesviruses are also regulated by cellular epigenetic machinery, and epigenetic therapeutics represent a novel approach used to control infection, persistence, and the resulting recurrent disease...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28808424/acetylation-of-hmof-modulates-h4k16ac-to-regulate-dna-repair-genes-in-response-to-oxidative-stress
#7
Jianing Zhong, Liying Ji, Huiqian Chen, Xianfeng Li, Jian'an Zhang, Xingxing Wang, Weilin Wu, Ying Xu, Fei Huang, Wanshi Cai, Zhong Sheng Sun
Oxidative stress is considered to be a key risk state for a variety of human diseases. In response to oxidative stress, the regulation of transcriptional expression of DNA repair genes would be important to DNA repair and genomic stability. However, the overall pattern of transcriptional expression of DNA repair genes and the underlying molecular response mechanism to oxidative stress remain unclear. Here, by employing colorectal cancer cell lines following exposure to hydrogen peroxide, we generated expression profiles of DNA repair genes via RNA-seq and identified gene subsets that are induced or repressed following oxidative stress exposure...
2017: International Journal of Biological Sciences
https://www.readbyqxmd.com/read/28808057/a-kidney-specific-genetic-control-module-in-mice-governs-endocrine-regulation-of-the-cytochrome-p450-gene-cyp27b1-essential-for-vitamin-d3-activation
#8
Mark B Meyer, Nancy A Benkusky, Martin Kaufmann, Seong Min Lee, Melda Onal, Glenville Jones, J Wesley Pike
The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D3 to its hormonal form, 1,25(OH)2D3, occurs in the kidney via the cytochrome P450 enzyme CYP27B1. Despite its importance in vitamin D metabolism, the molecular mechanisms underlying the regulation of the gene for this enzyme, Cyp27b1, are unknown. Here, we identified a kidney-specific control module governed by a renal cell-specific chromatin structure located distal to Cyp27b1 that mediates unique basal and parathyroid hormone (PTH)-, fibroblast growth factor 23 (FGF23)-, and 1,25(OH)2D3-mediated regulation of Cyp27b1 expression...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28807921/candida-albicans-swi-snf-and-mediator-complexes-differentially-regulate-mrr1-induced-mdr1-expression-and-fluconazole-resistance
#9
Zhongle Liu, Lawrence C Myers
Long-term azole treatment of patients with chronic Candida albicans infections can lead to drug resistance. Gain-of-function (GOF) mutations in the transcription factor Mrr1 and the consequent transcriptional activation of MDR1, a drug efflux coding gene, is a common pathway by which this human fungal pathogen acquires fluconazole resistance. This work elucidates the previously unknown downstream transcription mechanisms utilized by hyperactive Mrr1. We've identified the Swi/Snf chromatin remodeling complex as a key co-activator for Mrr1, which is required to maintain basal and induced 'open' chromatin, and Mrr1 occupancy, at the MDR1 promoter...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28807899/pitx1-directly-modulates-the-core-limb-development-program-to-implement-hindlimb-identity
#10
Stephen Nemec, Maëva Luxey, Deepak Jain, Aurélie Huang Sung, Tomi Pastinen, Jacques Drouin
Forelimbs (FL) and hindlimbs (HL) develop complex musculoskeletal structures that rely on the deployment of a conserved developmental program. Pitx1, a transcription factor gene with expression restricted to HL and absent from FL, plays an important role in generating HL features. The genomic mechanisms by which Pitx1 effects HL identity remain poorly understood, however. Here, we use expression profiling and analysis of direct Pitx1 targets to characterize the HL- and FL-restricted genetic programs and situate the Pitx1-dependent gene network within the context of limb-specific gene regulation...
August 14, 2017: Development
https://www.readbyqxmd.com/read/28801231/anti-inflammatory-chromatinscape-suggests-alternative-mechanisms-of-glucocorticoid-receptor-action
#11
Kyu-Seon Oh, Heta Patel, Rachel A Gottschalk, Wai Shing Lee, Songjoon Baek, Iain D C Fraser, Gordon L Hager, Myong-Hee Sung
Despite the widespread use of glucocorticoids (GCs), their anti-inflammatory effects are not understood mechanistically. Numerous investigations have examined the effects of glucocorticoid receptor (GR) activation prior to inflammatory challenges. However, clinical situations are emulated by a GC intervention initiated in the midst of rampant inflammatory responses. To characterize the effects of a late GC treatment, we profiled macrophage transcriptional and chromatinscapes with Dexamethasone (Dex) treatment before or after stimulation by lipopolysaccharide (LPS)...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28800870/recent-advances-in-her2-positive-breast-cancer-epigenetics-susceptibility-and-therapeutic-strategies
#12
REVIEW
Heena Singla, Abhilash Ludhiadch, Raman Preet Kaur, Harish Chander, Vinod Kumar, Anjana Munshi
HER2 amplification/overexpression accounts for aggressive clinical features of HER2 positive breast cancer. Epigenetic changes including DNA methylation, histone modifications and ncRNAs/miRNAs are associated with regulation of DNA chromatin and specifically, gene transcription. Hence, these produce eminent effects upon proto-oncogenes, tumor-suppressors and key cancer-regulatory signaling pathways. Understanding of epigenomic regulation of HER2 overexpression and signaling may help uncover the unmatchable physiology of HER2 gene/protein...
August 1, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28795861/lnc00673-errlr01-is-a-prognostic-indicator-of-overall-survival-in-breast-cancer
#13
Ubaidat Abdul-Rahman, Balázs Gyoörffy, Brian D Adams
LncRNAs are novel noncoding RNAs involved in the epigenetic regulation of gene expression by recruiting ribonucleoprotein complexes to specific genomic loci to initiate histone methylation and/or other chromatin modifications. LncRNAs themselves function as tumor suppressors or oncogenes, depending on the gene regulatory networks they govern. We identified lnc00673 (ERRLR01) as a marker of overall survival (OS) in breast cancer patients. Specifically, ERRLR01 levels were elevated in triple-negative breast cancer (TNBC) as compared to Luminal- A, Luminal-B, and HER2 breast cancer subtypes...
August 10, 2017: Transcription
https://www.readbyqxmd.com/read/28795356/drosophila-studies-on-autism-spectrum-disorders
#14
REVIEW
Yao Tian, Zi Chao Zhang, Junhai Han
In the past decade, numerous genes associated with autism spectrum disorders (ASDs) have been identified. These genes encode key regulators of synaptogenesis, synaptic function, and synaptic plasticity. Drosophila is a prominent model system for ASD studies to define novel genes linked to ASDs and decipher their molecular roles in synaptogenesis, synaptic function, synaptic plasticity, and neural circuit assembly and consolidation. Here, we review Drosophila studies on ASD genes that regulate synaptogenesis, synaptic function, and synaptic plasticity through modulating chromatin remodeling, transcription, protein synthesis and degradation, cytoskeleton dynamics, and synaptic scaffolding...
August 9, 2017: Neuroscience Bulletin
https://www.readbyqxmd.com/read/28794020/adenovirus-core-protein-vii-down-regulates-the-dna-damage-response-on-the-host-genome
#15
Daphne C Avgousti, Ashley N Della Fera, Clayton J Otter, Christin Herrmann, Neha J Pancholi, Matthew D Weitzman
Viral manipulation of cellular proteins allows viruses to suppress host defenses and generate infectious progeny. Due to the linear double-stranded DNA nature of the adenovirus genome, the cellular DNA damage response (DDR) is considered a barrier for successful infection. The adenovirus genome is packaged with protein VII, a viral-encoded histone-like core protein that is suggested to protect incoming viral genomes from detection by cellular DNA damage machinery. We showed that protein VII localizes to host chromatin during infection, leading us to hypothesize that protein VII may affect DNA damage responses on the cellular genome...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28790204/bacterial-chromatin-structural-proteins-regulate-the-bimodal-expression-of-the-locus-of-enterocyte-effacement-lee-pathogenicity-island-in-enteropathogenic-escherichia-coli
#16
Hervé Leh, Ahmad Khodr, Marie-Christine Bouger, Bianca Sclavi, Sylvie Rimsky, Stéphanie Bury-Moné
In enteropathogenic Escherichia coli (EPEC), the locus of enterocyte effacement (LEE) encodes a type 3 secretion system (T3SS) essential for pathogenesis. This pathogenicity island comprises five major operons (LEE1 to LEE5), with the LEE5 operon encoding T3SS effectors involved in the intimate adherence of bacteria to enterocytes. The first operon, LEE1, encodes Ler (LEE-encoded regulator), an H-NS (nucleoid structuring protein) paralog that alleviates the LEE H-NS silencing. We observed that the LEE5 and LEE1 promoters present a bimodal expression pattern, depending on environmental stimuli...
August 8, 2017: MBio
https://www.readbyqxmd.com/read/28790150/phosphorylation-of-histone-h2a-at-serine-95-a-plant-specific-mark-involved-in-flowering-time-regulation-and-h2a-z-deposition
#17
Yanhua Su, Shiliang Wang, Fei Zhang, Han Zheng, Yana Liu, Tongtong Huang, Yong Ding
Phosphorylation of histone H3 affects transcription, chromatin condensation, and chromosome segregation. However, the role of phosphorylation of histone H2A remains unclear. Here, we found that Arabidopsis thaliana MUT9P-LIKE-KINASE (MLK4) phosphorylates histone H2A on serine 95, a plant-specific modification in the histone core domain. Mutations in MLK4 caused late flowering under long-day conditions but no notable phenotype under short days. MLK4 interacts with CIRCADIAN CLOCK ASSOCIATED1 (CCA1), which allows MLK4 to bind to the GIGANTEA (GI) promoter...
August 8, 2017: Plant Cell
https://www.readbyqxmd.com/read/28780641/the-flexible-stem-hypothesis-evidence-from-genetic-data
#18
REVIEW
Jean-Michel Gibert
Phenotypic plasticity, the ability of a given genotype to produce different phenotypes in response to distinct environmental conditions, is widely observed in the wild. It is believed to facilitate evolution and, under the "flexible stem hypothesis", it is thought that an ancestral plastic species can be at the origin of sister lineages with divergent phenotypes fixed by genetic assimilation of alternative morphs. We review here the genetic mechanisms underlying such phenomenon. We show several examples in which the same gene shows transcriptional plasticity in response to environmental factors and divergence of expression within or between species...
August 6, 2017: Development Genes and Evolution
https://www.readbyqxmd.com/read/28778076/modulation-of-the-fanconi-anemia-pathway-via-chemically-induced-changes-in-chromatin-structure
#19
David A Vierra, Jada L Garzon, Meghan A Rego, Morganne M Adroved, Maurizio Mauro, Niall G Howlett
Fanconi anemia (FA) is a rare disease characterized by congenital defects, bone marrow failure, and atypically early-onset cancers. The FA proteins function cooperatively to repair DNA interstrand crosslinks. A major step in the activation of the pathway is the monoubiquitination of the FANCD2 and FANCI proteins, and their recruitment to chromatin-associated nuclear foci. The regulation and function of FANCD2 and FANCI, however, is poorly understood. In addition, how chromatin state impacts pathway activation is also unknown...
July 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28777932/long-noncoding-rnas-cupid1-and-cupid2-mediate-breast-cancer-risk-at-11q13-by-modulating-the-response-to-dna-damage
#20
Joshua A Betts, Mahdi Moradi Marjaneh, Fares Al-Ejeh, Yi Chieh Lim, Wei Shi, Haran Sivakumaran, Romain Tropée, Ann-Marie Patch, Michael B Clark, Nenad Bartonicek, Adrian P Wiegmans, Kristine M Hillman, Susanne Kaufmann, Amanda L Bain, Brian S Gloss, Joanna Crawford, Stephen Kazakoff, Shivangi Wani, Shu W Wen, Bryan Day, Andreas Möller, Nicole Cloonan, John Pearson, Melissa A Brown, Timothy R Mercer, Nicola Waddell, Kum Kum Khanna, Eloise Dray, Marcel E Dinger, Stacey L Edwards, Juliet D French
Breast cancer risk is strongly associated with an intergenic region on 11q13. We have previously shown that the strongest risk-associated SNPs fall within a distal enhancer that regulates CCND1. Here, we report that, in addition to regulating CCND1, this enhancer regulates two estrogen-regulated long noncoding RNAs, CUPID1 and CUPID2. We provide evidence that the risk-associated SNPs are associated with reduced chromatin looping between the enhancer and the CUPID1 and CUPID2 bidirectional promoter. We further show that CUPID1 and CUPID2 are predominantly expressed in hormone-receptor-positive breast tumors and play a role in modulating pathway choice for the repair of double-strand breaks...
August 3, 2017: American Journal of Human Genetics
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