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https://www.readbyqxmd.com/read/28329910/nucleosome-mobility-and-the-regulation-of-gene-expression-insights-from-single-molecule-studies
#1
REVIEW
Sergei Rudnizky, Omri Malik, Adaiah Bavly, Lilach Pnueli, Philippa Melamed, Ariel Kaplan
Nucleosomes at the promoters of genes regulate the accessibility of the transcription machinery to DNA, and function as a basic layer in the complex regulation of gene expression. Our understanding of the role of the nucleosome's spontaneous, thermally driven position changes in modulating expression is lacking. This is the result of the paucity of experimental data on these dynamics, at high-resolution, and for DNA sequences that belong to real, transcribed genes. We have developed an assay that uses partial, reversible unzipping of nucleosomes with optical tweezers to repeatedly probe a nucleosome's position over time...
March 22, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28329683/inactivation-of-ezh2-upregulates-gfi1-and-drives-aggressive-myc-driven-group-3-medulloblastoma
#2
BaoHan T Vo, Chunliang Li, Marc A Morgan, Ilan Theurillat, David Finkelstein, Shaela Wright, Judith Hyle, Stephanie M C Smith, Yiping Fan, Yong-Dong Wang, Gang Wu, Brent A Orr, Paul A Northcott, Ali Shilatifard, Charles J Sherr, Martine F Roussel
The most aggressive of four medulloblastoma (MB) subgroups are cMyc-driven group 3 (G3) tumors, some of which overexpress EZH2, the histone H3K27 mono-, di-, and trimethylase of polycomb-repressive complex 2. Ezh2 has a context-dependent role in different cancers as an oncogene or tumor suppressor and retards tumor progression in a mouse model of G3 MB. Engineered deletions of Ezh2 in G3 MBs by gene editing nucleases accelerated tumorigenesis, whereas Ezh2 re-expression reversed attendant histone modifications and slowed tumor progression...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28328977/jmjd3-aids-in-reprogramming-of-bone-marrow-progenitor-cells-to-hepatic-phenotype-through-epigenetic-activation-of-hepatic-transcription-factors
#3
Veena Kochat, Zaffar Equbal, Prakash Baligar, Vikash Kumar, Madhulika Srivastava, Asok Mukhopadhyay
The strictly regulated unidirectional differentiation program in some somatic stem/progenitor cells has been found to be modified in the ectopic site (tissue) undergoing regeneration. In these cases, the lineage barrier is crossed by either heterotypic cell fusion or direct differentiation. Though studies have shown the role of coordinated genetic and epigenetic mechanisms in cellular development and differentiation, how the lineage fate of adult bone marrow progenitor cells (BMPCs) is reprogrammed during liver regeneration and whether this lineage switch is stably maintained are not clearly understood...
2017: PloS One
https://www.readbyqxmd.com/read/28328153/behavioral-transcriptomic-and-epigenetic-responses-to-social-challenge-in-honey-bees
#4
Hagai Y Shpigler, Michael C Saul, Emma E Murdoch, Amy C Cash-Ahmed, Christopher H Seward, Laura Sloofman, Sriram Chandrasekaran, Saurabh Sinha, Lisa J Stubbs, Gene E Robinson
Understanding how social experiences are represented in the brain and shape future responses is a major challenge in the study of behavior. We addressed this problem by studying behavioral, transcriptomic and epigenetic responses to intrusion in honey bees. Previous research showed that initial exposure to an intruder provokes an immediate attack; we now show that this also leads to longer-term changes in behavior in the response to a second intruder, with increases in the probability of responding aggressively and the intensity of aggression lasting two and one hours, respectively...
March 22, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28327630/rassf-proteins-as-modulators-of-mst1-kinase-activity
#5
Aruna Bitra, Srinivas Sistla, Jessy Mariam, Harshada Malvi, Ruchi Anand
Rassf1A/5 tumor suppressors serve as adaptor proteins possessing a modular architecture with the C-terminal consisting of a coiled-coil SARAH (Salvador-Rassf-Hippo) domain and the central portion being composed of Ras associated (RA) domain. Here, we investigate the effect of Rassf effectors on Mst1 function by mapping the interaction of various domains of Rassf1A/5 and Mst1 kinase using surface plasmon resonance (SPR). The results revealed that apart from the C-terminal SARAH domain of Mst1 which interacts to form heterodimers with Rassf1A/5, the N-terminal kinase domain of Mst1 plays a crucial role in the stabilization of this complex...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327608/kdm4b-histone-demethylase-and-g9a-regulate-expression-of-vascular-adhesion-proteins-in-cerebral-microvessels
#6
Ji-Young Choi, Sang-Sun Yoon, Sang-Eun Kim, Sangmee Ahn Jo
Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28327192/dna-double-strand-breaks-in-human-induced-pluripotent-stem-cell-reprogramming-and-long-term-in-vitro-culturing
#7
Pavel Simara, Lenka Tesarova, Daniela Rehakova, Pavel Matula, Stanislav Stejskal, Ales Hampl, Irena Koutna
BACKGROUND: Human induced pluripotent stem cells (hiPSCs) play roles in both disease modelling and regenerative medicine. It is critical that the genomic integrity of the cells remains intact and that the DNA repair systems are fully functional. In this article, we focused on the detection of DNA double-strand breaks (DSBs) by phosphorylated histone H2AX (known as γH2AX) and p53-binding protein 1 (53BP1) in three distinct lines of hiPSCs, their source cells, and one line of human embryonic stem cells (hESCs)...
March 21, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28326943/analgesia-induced-by-the-epigenetic-drug-l-acetylcarnitine-outlasts-the-end-of-treatment-in-mouse-models-of-chronic-inflammatory-and-neuropathic-pain
#8
Serena Notartomaso, Giada Mascio, Matteo Bernabucci, Cristina Zappulla, Pamela Scarselli, Milena Cannella, Tiziana Imbriglio, Roberto Gradini, Giuseppe Battaglia, Valeria Bruno, Ferdinando Nicoletti
Background L-acetylcarnitine, a drug marketed for the treatment of chronic pain, causes analgesia by epigenetically up-regulating type-2 metabotropic glutamate (mGlu2) receptors in the spinal cord. Because the epigenetic mechanisms are typically long-lasting, we hypothesized that analgesia could outlast the duration of L-acetylcarnitine treatment in models of inflammatory and neuropathic pain. Results A seven-day treatment with L-acetylcarnitine (100 mg/kg, once a day, i.p.) produced an antiallodynic effect in the complete Freund adjuvant mouse model of chronic inflammatory pain...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28326839/entinostat-a-promising-treatment-option-for-patients-with-advanced-breast-cancer
#9
Roisin M Connolly, Michelle A Rudek, Richard Piekarz
Entinostat is a synthetic benzamide derivative histone deacetylase (HDAC) inhibitor, which potently and selectively inhibits class I and IV HDAC enzymes. This action promotes histone hyperacetylation and transcriptional activation of specific genes, with subsequent inhibition of cell proliferation, terminal differentiation and apoptosis. This oral HDAC inhibitor has been evaluated in Phase I and II trials in patients with advanced malignancies, and is in general well tolerated. Entinostat does not currently have regulatory approval for clinical use; however promising preclinical and clinical data exist in hormone-resistant breast cancer...
March 9, 2017: Future Oncology
https://www.readbyqxmd.com/read/28326594/hypoacetylation-of-acetyl-histone-h3-h3k9ac-as-marker-of-poor-prognosis-in-oral-cancer
#10
Liana Preto Webber, Vivian Petersen Wagner, Marina Curra, Pablo Agustin Vargas, Luise Meurer, Vinícius Coelho Carrard, Cristiane Helena Squarize, Rogério Moraes Castilho, Manoela Domingues Martins
AIMS: Epigenetics refers to changes in cell characteristics that occur independently of modifications to the DNA sequence. Oral carcinogenesis is influenced by modifications in epigenetic mechanisms, including changes in histones, which are proteins that support chromatin remodeling for the dynamic regulation of gene expression and silencing. The dysregulation of histone acetylation can lead to the uncontrolled activity of different genes, thereby triggering events associated with malignant transformation...
March 22, 2017: Histopathology
https://www.readbyqxmd.com/read/28326191/global-histone-modification-fingerprinting-in-human-cells-using-epigenetic-reverse-phase-protein-array
#11
Marina Partolina, Hazel C Thoms, Kenneth G MacLeod, Giovanny Rodriguez-Blanco, Matthew N Clarke, Anuroop V Venkatasubramani, Rima Beesoo, Vladimir Larionov, Vidushi S Neergheen-Bhujun, Bryan Serrels, Hiroshi Kimura, Neil O Carragher, Alexander Kagansky
The balance between acetylation and deacetylation of histone proteins plays a critical role in the regulation of genomic functions. Aberrations in global levels of histone modifications are linked to carcinogenesis and are currently the focus of intense scrutiny and translational research investments to develop new therapies, which can modify complex disease pathophysiology through epigenetic control. However, despite significant progress in our understanding of the molecular mechanisms of epigenetic machinery in various genomic contexts and cell types, the links between epigenetic modifications and cellular phenotypes are far from being clear...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28326190/malat1-regulates-myogenic-differentiation-and-muscle-regeneration-through-modulating-myod-transcriptional-activity
#12
Xiaona Chen, Liangqiang He, Yu Zhao, Yuying Li, Suyang Zhang, Kun Sun, Karl So, Fengyuan Chen, Liang Zhou, Leina Lu, Lijun Wang, Xihua Zhu, Xichen Bao, Miguel A Esteban, Shinichi Nakagawa, Kannanganattu V Prasanth, Zhenguo Wu, Hao Sun, Huating Wang
Malat1 is one of the most abundant long non-coding RNAs in various cell types; its exact cellular function is still a matter of intense investigation. In this study we characterized the function of Malat1 in skeletal muscle cells and muscle regeneration. Utilizing both in vitro and in vivo assays, we demonstrate that Malat1 has a role in regulating gene expression during myogenic differentiation of myoblast cells. Specifically, we found that knockdown of Malat1 accelerates the myogenic differentiation in cultured cells...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28326018/neuronal-nitric-oxide-synthase-in-neural-stem-cells-induces-neuronal-fate-commitment-via-the-inhibition-of-histone-deacetylase-2
#13
Xing Jin, Zhang-Feng Yu, Fang Chen, Guang-Xian Lu, Xin-Yuan Ding, Lin-Jun Xie, Jian-Tong Sun
Active adult neurogenesis produces new functional neurons, which replace the lost ones and contribute to brain repair. Promoting neurogenesis may offer a therapeutic strategy for human diseases associated with neurodegeneration. Here, we report that endogenous neuronal nitric oxide synthase (nNOS) for neural stem cells (NSCs) or progenitors positively regulates neurogenesis. nNOS repression exhibits significantly decreased neuronal differentiation and nNOS upregulation promotes neurons production from NSCs...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28325302/aptamer-drug-conjugates-of-active-metabolites-of-nucleoside-analogs-and-cytotoxic-agents-inhibit-pancreatic-tumor-cell-growth
#14
Sorah Yoon, Kai-Wen Huang, Vikash Reebye, Duncan Spalding, Teresa M Przytycka, Yijie Wang, Piotr Swiderski, Lin Li, Brian Armstrong, Isabella Reccia, Dimitris Zacharoulis, Konstantinos Dimas, Tomokazu Kusano, John Shively, Nagy Habib, John J Rossi
Aptamer-drug conjugates (ApDCs) have the potential to improve the therapeutic index of traditional chemotherapeutic agents due to their ability to deliver cytotoxic drugs specifically to cancer cells while sparing normal cells. This study reports on the conjugation of cytotoxic drugs to an aptamer previously described by our group, the pancreatic cancer RNA aptamer P19. To this end, P19 was incorporated with gemcitabine and 5-fluorouracil (5-FU), or conjugated to monomethyl auristatin E (MMAE) and derivative of maytansine 1 (DM1)...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28325256/how-have-evolutions-in-strategies-for-the-treatment-of-relapsed-refractory-multiple-myeloma-translated-into-improved-outcomes-for-patients
#15
REVIEW
Pieter Sonneveld, Edwin De Wit, Philippe Moreau
Although multiple myeloma (MM) remains incurable, the introduction of novel agents has improved clinical outcomes dramatically over the past 15 years. Response rates have risen from ∼30% with single agents to up to 90% with combination therapies. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide, and the proteasome inhibitor bortezomib, form the foundations for treatment of relapsed and/or refractory MM (RRMM). Newer agents, such as the IMiD pomalidomide, the histone deacetylase inhibitor panobinostat and the proteasome inhibitors carfilzomib and ixazomib, as well as the monoclonal antibodies daratumumab and elotuzumab, have further improved overall response rates in these patients...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28324153/epigenetics-in-the-pathogenesis-of-ra
#16
REVIEW
Caroline Ospelt, Steffen Gay, Kerstin Klein
Epigenetic modifications can stably alter gene expression and have been shown to be important in the maintenance of cell type-specific functions as well as in cell differentiation, e.g., in T and B cell maturation. In RA, alterations in DNA methylation, histone modifications, and microRNA expression have been found in immune as well as in stromal cells. These changes in the epigenome in RA patients influence key inflammatory and matrix-degrading pathways and are suspected to play a major role in the pathogenesis of RA...
March 21, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28324105/thyroid-hormone-dependent-epigenetic-regulation-of-melanocortin-4-receptor-levels-in-female-offspring-of-obese-rats
#17
T Tabachnik, T Kisliouk, A Marco, N Meiri, A Weller
Maternal obesity is a risk factor for offspring obesity. Melanocortin 4 receptor (Mc4r) is one of the mediators of food intake and energy balance. This study examines epigenetic mechanisms underlying altered Mc4r levels in the hypothalamic paraventricular nucleus in offspring of high-fat diet (HFD)-induced obese dams, and aims to elucidate the role of thyroid hormones in epigenetic regulation and tagging of their nucleosome at the Mc4r promoter. Female Wistar rats were fed HFD or chow from weaning through gestation and lactation...
January 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28324044/inverse-regulation-of-dht-synthesis-enzymes-5%C3%AE-reductase-types-1-and-2-by-the-androgen-receptor-in-prostate-cancer
#18
Étienne Audet-Walsh, Tracey Yee, Ingrid S Tam, Vincent Giguère
5α-reductase types 1 and 2, encoded by SRD5A1 and SRD5A2, are the two enzymes that can catalyze the conversion of testosterone to dihydrotestosterone, the most potent androgen receptor (AR) agonist in prostate cells. 5α-reductase type 2 is the predominant isoform expressed in the normal prostate. However, its expression decreases during prostate cancer (PCa) progression, while SRD5A1 increases and the mechanism underlying this transcriptional regulatory switch is still unknown. Interrogation of SRD5A mRNA expression in three publicly available datasets confirmed that SRD5A1 is increased in primary and metastatic PCa compared to non-tumoral prostate tissues, while SRD5A2 is decreased...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323958/jmjd3-is-crucial-for-female-avpv-rip-cre-neuron-controlled-kisspeptin-estrogen-feedback-loop-and-reproductive-function
#19
Anying Song, Shujun Jiang, Qinghua Wang, Jianghuan Zou, Zhaoyu Lin, Xiang Gao
The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. While most studies were focusing on the hierarch from brain to gonad, many questions remain unresolved concerning the feedback from gonad to the central nervous system, especially on the potential epigenetic modification in hypothalamic neurons. In this report, we generated genetically modified mice lacking histone H3 lysine 27 demethylase JMJD3 in hypothalamic RIP-Cre neurons. The female mutant mice display late-onset obesity due to reduced locomotor activity and decreased energy expenditure...
March 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323522/detection-of-cytosine-and-cpg-density-in-proto-oncogenes-and-tumor-suppressor-genes-in-promoter-sequences-of-acute-myeloid-leukemia
#20
Senol Dogan, Anis Cilic, Damir Marjanovic, Amina Kurtovic-Kozaric
Aberrant methylation is one of the driving forces of cancer genome development. Although the rate of methylation appears massively variable across the genome, it is mainly observed in histone modification, chromatin organization, DNA accessibility, or promoter sequence. Methylation of promoter sequence occurs mostly to cytosine nucleotides, which can affect transcription factors' binding affinities. In this study, we demonstrated that cytosine repeats (C types density), consisting of CC, CCC, CCCC, CCCCC, CCCCCC, CCCCCCC motifs and CpG islands density in 25 proto-oncogenes, tumor suppressor genes and control genes may play a role in the pathogenesis of acute myeloid leukemia...
March 21, 2017: Nucleosides, Nucleotides & Nucleic Acids
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