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https://www.readbyqxmd.com/read/28644137/analyses-of-germline-variants-associated-with-ovarian-cancer-survival-identify-functional-candidates-at-the-1q22-and-19p12-outcome-loci
#1
Dylan M Glubb, Sharon E Johnatty, Michael C J Quinn, Tracy A O'Mara, Jonathan P Tyrer, Bo Gao, Peter A Fasching, Matthias W Beckmann, Diether Lambrechts, Ignace Vergote, Digna R Velez Edwards, Alicia Beeghly-Fadiel, Javier Benitez, Maria J Garcia, Marc T Goodman, Pamela J Thompson, Thilo Dörk, Matthias Dürst, Francesmary Modungo, Kirsten Moysich, Florian Heitz, Andreas du Bois, Jacobus Pfisterer, Peter Hillemanns, Beth Y Karlan, Jenny Lester, Ellen L Goode, Julie M Cunningham, Stacey J Winham, Melissa C Larson, Bryan M McCauley, Susanne Krüger Kjær, Allan Jensen, Joellen M Schildkraut, Andrew Berchuck, Daniel W Cramer, Kathryn L Terry, Helga B Salvesen, Line Bjorge, Penny M Webb, Peter Grant, Tanja Pejovic, Melissa Moffitt, Claus K Hogdall, Estrid Hogdall, James Paul, Rosalind Glasspool, Marcus Bernardini, Alicia Tone, David Huntsman, Michelle Woo, Aocs Group, Anna deFazio, Catherine J Kennedy, Paul D P Pharoah, Stuart MacGregor, Georgia Chenevix-Trench
We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28641467/green-tea-polyphenol-egcg-causes-anti-cancerous-epigenetic-modulations-in-acute-promyelocytic-leukemia-cells
#2
Veronika Borutinskaitė, Aida Virkšaitė, Giedrė Gudelytė, Rūta Navakauskienė
Green tea (Camellia sinensis) catechin epigallocatechin-3-gallate (EGCG) has been shown to possess diverse anti-cancerous properties. We demonstrated EGCG ability to inhibit acute promyelocytic leukemia (APL) cell proliferation and cause apoptosis. In addition, quantitative real-time polymerase chain reaction (RT-qPCR) analysis revealed elevated expression of genes associated with cell cycle arrest and differentiation (p27, PCAF, C/EBPα, and C/EBPɛ). Furthermore, EGCG caused anti-cancerous epigenetic changes: downregulation of epigenetic modifiers DNMT1, HDAC1, HDAC2, and G9a was observed by RT-qPCR analysis...
June 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28637297/a-role-for-progesterone-regulated-sfrp4-expression-in-uterine-leiomyomas
#3
Meaghan A Delaney, Ying-Wooi Wan, Gyoung-Eun Kim, Chad J Creighton, Margaret G Taylor, Ramya Masand, Andrew Park, Cecilia Valdes, William Gibbons, Zhandong Liu, Matthew L Anderson
Context: Despite progesterone's key role in uterine smooth muscle tumorigenesis, the mechanisms by which it promotes the growth of uterine leiomyomas remain poorly understood. Objective: The aim of this study was to identify novel gene products mediating progesterone's effects in uterine leiomyomas. Design: Gene expression profiling was used to identify putative progesterone-regulated genes differentially expressed in uterine leiomyomas, which were then studied in vitro...
June 14, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28626222/the-role-of-epigenetics-in-renal-ageing
#4
REVIEW
Paul G Shiels, Dagmara McGuinness, Maria Eriksson, Jeroen P Kooman, Peter Stenvinkel
An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin...
June 19, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28621413/the-sumo-system-in-caenorhabditis-elegans-development
#5
Limor Broday
SUMO, a small ubiquitin-like modifier, is a highly conserved post translational modification and a central regulatory system in eukaryotes. Sumoylation modulates the activities of multiple proteins, mainly in the nucleus, such as transcription factors, chromatin modifiers, and proteins involved in DNA replication and repair. However, SUMO also modifies substrates in the cytoplasm, mitochondria, plasma and ER membrane. This review summarizes our current knowledge on the functions of sumoylation in C. elegans development...
2017: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/28619818/antagonistic-regulation-of-the-second-mitotic-wave-by-eyes-absent-sine-oculis-and-combgap-coordinates-proliferation-and-specification-in-the-drosophila-retina
#6
Trevor L Davis, Ilaria Rebay
The transition from proliferation to specification is fundamental to the development of appropriately patterned tissues. In the developing Drosophila eye, Eyes absent (Eya) and Sine oculis (So) orchestrate the progression of progenitor cells from asynchronous cell division to G1 arrest and neuronal specification at the morphogenetic furrow. Here, we uncover a novel role for Eya and So in promoting cell cycle exit in the Second Mitotic Wave (SMW), a synchronized, terminal cell division that occurs several hours after passage of the furrow...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28619072/the-arabidopsis-swi-snf-protein-baf60-mediates-seedling-growth-control-by-modulating-dna-accessibility
#7
Teddy Jégu, Alaguraj Veluchamy, Juan S Ramirez-Prado, Charley Rizzi-Paillet, Magalie Perez, Anaïs Lhomme, David Latrasse, Emeline Coleno, Serge Vicaire, Stéphanie Legras, Bernard Jost, Martin Rougée, Fredy Barneche, Catherine Bergounioux, Martin Crespi, Magdy M Mahfouz, Heribert Hirt, Cécile Raynaud, Moussa Benhamed
BACKGROUND: Plant adaptive responses to changing environments involve complex molecular interplays between intrinsic and external signals. Whilst much is known on the signaling components mediating diurnal, light, and temperature controls on plant development, their influence on chromatin-based transcriptional controls remains poorly explored. RESULTS: In this study we show that a SWI/SNF chromatin remodeler subunit, BAF60, represses seedling growth by modulating DNA accessibility of hypocotyl cell size regulatory genes...
June 15, 2017: Genome Biology
https://www.readbyqxmd.com/read/28618937/37lrp-induces-invasion-in-hypoxic-lung-adenocarcinoma-cancer-cells-a549-through-the-jnk-erk-c-jun-signaling-cascade
#8
Yongan Zhou, Yafang Wang, Zhengwei Zhao, Yanxia Wang, Ning Zhang, Helong Zhang, Lili Liu
We previously reported that 37-kDa laminin receptor precursor involved in metastasis of lung adenocarcinoma cancer cells. In this study, we further revealed that hypoxia induced 37-kDa laminin receptor precursor expression and activation of extracellular signal-regulated protein kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase in lung adenocarcinoma cancer cells. In addition, we further demonstrated that the c-Jun N-terminal kinase inhibitor SP600125 and extracellular signal-regulated protein kinase inhibitor U0126 blocked the c-Jun activity and abolished hypoxia-induced 37-kDa laminin receptor precursor expression and promoter activity in a concentration-dependent manner...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28617821/supplementation-with-small-extracellular-vesicles-from-ovarian-follicular-fluid-during-in-vitro-production-modulates-bovine-embryo-development
#9
Juliano C da Silveira, Gabriella M Andrade, Maite Del Collado, Rafael V Sampaio, Juliano R Sangalli, Luciano A Silva, Fábio V L Pinaffi, Izabelle B Jardim, Marcelo C Cesar, Marcelo F G Nogueira, Aline S M Cesar, Luiz L Coutinho, Rinaldo W Pereira, Felipe Perecin, Flávio V Meirelles
Pregnancy success results from the interaction of multiple factors, among them are folliculogenesis and early embryonic development. Failure during these different processes can lead to difficulties in conception. Alternatives to overcome these problems are based on assisted reproductive techniques. Extracellular vesicles are cell-secreted vesicles present in different body fluids and contain bioactive materials, such as messenger RNA, microRNAs (miRNAs), and proteins. Thus, our hypothesis is that extracellular vesicles from follicular fluid from 3-6 mm ovarian follicles can modulate bovine embryo development in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28615453/lncrnas-and-their-transcriptional-control-of-inflammatory-responses
#10
Nicholas W Mathy, Xian-Ming Chen
Long non-coding RNAs (lncRNAs) have emerged as potential key regulators of the inflammatory response, particularly by modulating the transcriptional control of inflammatory genes. LncRNAs may act as an enhancer or suppressor to inflammatory transcription, function as scaffold molecules through interactions with RNA-binding proteins in chromatin remodeling complexes, and modulate dynamic and epigenetic control of inflammatory transcription in a gene-specific and time-dependent fashion. Here, we will review recent literature regarding the role of lncRNAs in transcriptional control of inflammatory responses...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28615201/the-latency-associated-nuclear-antigen-of-kaposi-s-sarcoma-associated-herpesvirus-inhibits-expression-of-sumo-sentrin-specific-peptidase-6-to-facilitate-latency-establishment
#11
Xiaoxi Lin, Rui Sun, Fang Zhang, Yuan Gao, Lianghua Bin, Ke Lan
Kaposi's sarcoma-associated herpesvirus (KSHV), belonging to γ-herpesviridae, typically displays two different phases in its lifecycle, the latent phase and the lytic phase. Latent-associated nuclear antigen (LANA), the primary viral product during latency, has been reported to bind to a series of cellular gene promoters to modulate gene transcription. To systemically elucidate the cellular genes regulated by LANA, we identified genome-wide LANA binding sites by chromatin immunoprecipitation coupled with sequencing (ChIP-seq)...
June 14, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28613211/role-of-simvastatin-and-ror%C3%AE-activity-in-the-macrophage-apoptotic-pathway
#12
Neslihan Çoban, Çağrı Güleç, Bilge Özsait Selçuk, Nihan Erginel-Ünaltuna
OBJECTIVE: Atherosclerosis is a chronic inflammatory condition and is one of the main causes of death worldwide. Macrophages play important roles in the formation of atherosclerotic plaques. Apoptosis is progressively observed while plaques develop, although the precise mechanisms and outcomes of apoptosis in atherosclerosis development and progression are still contradictory. This study was conducted to explore the effects of simvastatin and retinoic acid receptor-related orphan receptor alpha (RORα) ligands on apoptosis in human acute monocytic leukemia (THP-1) macrophage cells...
May 2017: Anatolian Journal of Cardiology
https://www.readbyqxmd.com/read/28612091/intracellular-vorinostat-accumulation-and-its-relationship-to-histone-deacetylase-activity-in-soft-tissue-sarcoma-patients
#13
Jürgen Burhenne, Lu Liu, Christoph E Heilig, Andreas D Meid, Margarete Leisen, Thomas Schmitt, Bernd Kasper, Walter E Haefeli, Gerd Mikus, Gerlinde Egerer
PURPOSE: In the regulation of chromatin-structure and histone function, histone deacetylases (HDACs) are key enzymes and thus modulators of epigenetic regulation and gene expression. Accesses of the HDAC inhibitor vorinostat to intracellular compartments are essential to exert epigenetic effects. METHODS: In ten sarcoma patients receiving oral Zolinza (400 mg qd) vorinostat concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were quantified using validated LC/MS/MS assays to determine intracellular and extracellular pharmacokinetic data...
June 13, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28611940/involvement-of-chromatin-remodeling-genes-and-the-rho-gtpases-rhob-and-cdc42-in-ovarian-clear-cell-carcinoma
#14
Nicolai Skovbjerg Arildsen, Jenny-Maria Jönsson, Katarina Bartuma, Anna Ebbesson, Sofia Westbom-Fremer, Anna Måsbäck, Susanne Malander, Mef Nilbert, Ingrid A Hedenfalk
OBJECTIVE: Ovarian clear cell carcinomas (OCCCs) constitute a rare ovarian cancer subtype with distinct clinical features, but may nonetheless be difficult to distinguish morphologically from other subtypes. There is limited knowledge of genetic events driving OCCC tumorigenesis beyond ARID1A, which is reportedly mutated in 30-50% of OCCCs. We aimed to further characterize OCCCs by combined global transcriptional profiling and targeted deep sequencing of a panel of well-established cancer genes...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28611417/direct-evidence-for-cell-adhesion-mediated-radioresistance-cam-rr-on-the-level-of-individual-integrin-%C3%AE-1-clusters
#15
Laura Babel, Miriam Grunewald, Robert Lehn, Markus Langhans, Tobias Meckel
The cellular interaction with the extracellular matrix (ECM) modulates many key processes such as proliferation, migration, differentiation and survival. In addition, cells cultured under 3D conditions in presence of an ECM display a marked radioresistance towards ionizing radiation (IR) in comparison to conventionally 2D cultured cells. This process, also known as "cell-adhesion-mediated-radio-resistance" (CAM-RR), has been linked to the chromatin structure that differs between cells cultured on stiff surfaces versus cell grown on soft planar supports or in 3D environments...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611287/vorinostat-suppresses-hypoxia-signaling-by-modulating-nuclear-translocation-of-hypoxia-inducible-factor-1-alpha
#16
Chao Zhang, Chunzhang Yang, Michael J Feldman, Herui Wang, Ying Pang, Dominic M Maggio, Dongwang Zhu, Cody L Nesvick, Pauline Dmitriev, Petra Bullova, Prashant Chittiboina, Roscoe O Brady, Karel Pacak, Zhengping Zhuang
Histone deacetylase inhibitors (HDACis) are a potent class of tumor-suppressive agents traditionally believed to exert their effects through loosening tightly-wound chromatin resulting in de-inhibition of various tumor suppressive genes. Recent literature however has shown altered intratumoral hypoxia signaling with HDACi administration not attributable to changes in chromatin structure. We sought to determine the precise mechanism of HDACi-mediated hypoxia signaling attenuation using vorinostat (SAHA), an FDA-approved class I/IIb/IV HDACi...
May 23, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611266/retinoid-x-receptor-%C3%AE-dependent-hbv-minichromosome-remodeling-and-viral-replication
#17
Yan Zhang, Song He, Jin-Jun Guo, Hong Peng, Jia-Hao Fan, Qing-Ling Li
BACKGROUND AND AIM: The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor α (RXRα), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. MATERIAL AND METHODS: This study investigated RXRα involvement in HBV cccDNA epigenetic modifications...
August 1, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/28611184/regulation-of-the-ubiquitylation-and-deubiquitylation-of-creb-binding-protein-modulates-histone-acetylation-and-lung-inflammation
#18
Jianxin Wei, Su Dong, Rachel K Bowser, Andrew Khoo, Lina Zhang, Anastasia M Jacko, Yutong Zhao, Jing Zhao
Cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB)-binding protein (CBP) is a histone acetyltransferase that plays a pivotal role in the control of histone modification and the expression of cytokine-encoding genes in inflammatory diseases, including sepsis and lung injury. We found that the E3 ubiquitin ligase subunit FBXL19 targeted CBP for site-specific ubiquitylation and proteasomal degradation. The ubiquitylation-dependent degradation of CBP reduced the extent of lipopolysaccharide (LPS)-dependent histone acetylation and cytokine release in mouse lung epithelial cells and in a mouse model of sepsis...
June 13, 2017: Science Signaling
https://www.readbyqxmd.com/read/28604753/let-7b-and-let-7c-micrornas-promote-histone-h2b-ubiquitylation-and-inhibit-cell-migration-by-targeting-multiple-components-of-the-h2b-deubiquitylation-machinery
#19
A Spolverini, G Fuchs, D R Bublik, M Oren
Monoubiquitylation of histone H2B (H2Bub1) is catalyzed mainly by the RNF20/RNF40 complex and erased by multiple deubiquitylating enzymes (DUBs). H2Bub1 influences many aspects of chromatin function, including transcription regulation and DNA repair. Cancer cells often display reduced levels of H2Bub1, and this reduction may contribute to cancer progression. The let-7 family of microRNAs (miRNAs) comprises multiple members with reported tumor-suppressive features, whose expression is frequently downregulated in cancer...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28604691/ino80-exchanges-h2a-z-for-h2a-by-translocating-on-dna-proximal-to-histone-dimers
#20
Sandipan Brahma, Maheshi I Udugama, Jongseong Kim, Arjan Hada, Saurabh K Bhardwaj, Solomon G Hailu, Tae-Hee Lee, Blaine Bartholomew
ATP-dependent chromatin remodellers modulate nucleosome dynamics by mobilizing or disassembling nucleosomes, as well as altering nucleosome composition. These chromatin remodellers generally function by translocating along nucleosomal DNA at the H3-H4 interface of nucleosomes. Here we show that, unlike other remodellers, INO80 translocates along DNA at the H2A-H2B interface of nucleosomes and persistently displaces DNA from the surface of H2A-H2B. DNA translocation and DNA torsional strain created near the entry site of nucleosomes by INO80 promotes both the mobilization of nucleosomes and the selective exchange of H2A...
June 12, 2017: Nature Communications
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