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https://www.readbyqxmd.com/read/28316325/silencing-of-the-small-gtpase-diras3-induces-cellular-senescence-in-human-white-adipose-stromal-progenitor-cells
#1
Asim Ejaz, Monika Mattesich, Werner Zwerschke
Inhibition of Akt-mTOR signaling protects from obesity and extends life span in animals. In the present study, we analyse the impact of the small GTPase, GTP-binding RAS-like 3 (DIRAS3), a recently identified weight-loss target gene, on cellular senescence in adipose stromal/progenitor cells (ASCs) derived from human subcutaneous white adipose tissue (sWAT). We demonstrate that DIRAS3 knock-down (KD) in ASCs induces activation of Akt-mTOR signaling and proliferation arrest. DIRAS3 KD ASCs lose the potential to form colonies and are negative for Ki-67...
March 17, 2017: Aging
https://www.readbyqxmd.com/read/28315825/effects-of-florida-red-tides-on-histone-variant-expression-and-dna-methylation-in-the-eastern-oyster-crassostrea-virginica
#2
Rodrigo Gonzalez-Romero, Victoria Suarez-Ulloa, Javier Rodriguez-Casariego, Daniel Garcia-Souto, Gabriel Diaz, Abraham Smith, Juan Jose Pasantes, Gary Rand, Jose M Eirin-Lopez
Massive algal proliferations known as Harmful Algal Blooms (HABs) represent one of the most important threats to coastal areas. Among them, the so-called Florida Red Tides (FRTs, caused by blooms of the dinoflagellate Karenia brevis and associated brevetoxins) are particularly detrimental in the southeastern U.S., causing high mortality rates and annual losses in excess of $40 million. The ability of marine organisms to cope with environmental stressors (including those produced during HABs) is influenced by genetic and epigenetic mechanisms, the latter resulting in phenotypic changes caused by heritable modifications in gene expression, without involving changes in the genetic (DNA) sequence...
March 7, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28304275/pcgf6-prc1-suppresses-premature-differentiation-of-mouse-embryonic-stem-cells-by-regulating-germ-cell-related-genes
#3
Mitsuhiro Endoh, Takaho A Endo, Jun Shinga, Katsuhiko Hayashi, Anca Farcas, Kit-Wan Ma, Shinsuke Ito, Jafar Sharif, Tamie Endoh, Naoko Onaga, Manabu Nakayama, Tomoyuki Ishikura, Osamu Masui, Benedikt M Kessler, Toshio Suda, Osamu Ohara, Akihiko Okuda, Robert J Klose, Haruhiko Koseki
The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability...
March 17, 2017: ELife
https://www.readbyqxmd.com/read/28301306/two-possible-modes-of-pioneering-associated-with-combinations-of-h2a-z-and-p300-cbp-at-nucleosome-occupied-enhancers
#4
Pierre Cauchy, Frederic Koch, Jean-Christophe Andrau
Pioneer transcription factors are defined by their ability to bind nucleosome-occupied regions. Here, we discuss the properties of nucleosomes bound by pioneers at enhancer regions. We describe how select pioneers bind nucleosome-occupied or -depleted enhancer sites. Importantly, by revisiting and expanding existing data sets, we show differential H2A.Z and p300/CBP association at bound enhancers, highlighting two possible pioneering modes.
February 13, 2017: Transcription
https://www.readbyqxmd.com/read/28298436/chromatin-remodeler-chd4-represses-aberrant-expression-of-tbx3-and-sustains-self-renewal-of-embryonic-stem-cells
#5
Haixin Zhao, Zhijun Han, Xinyuan Liu, Junjie Gu, Fan Tang, Gang Wei, Ying Jin
The unique properties of embryonic stem cells (ESCs), unlimited self-renewal and pluripotent differentiation potential, are sustained by integrated genetic and epigenetic networks composed of a series of transcriptional factors and epigenetic modulators. However, molecular mechanisms underlying the function of these regulators are not fully elucidated. Chd4, an ATPase subunit of the nucleosome remodeling and deacetylase (NuRD) complex, is highly expressed in ESCs. However, its function in the regulation of ESC properties remains elusive...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28295392/erecta-signaling-controls-arabidopsis-inflorescence-architecture-through-chromatin-mediated-activation-of-pre1-expression
#6
Hanyang Cai, Lihua Zhao, Lulu Wang, Man Zhang, Zhenxia Su, Yan Cheng, Heming Zhao, Yuan Qin
Flowering plants display a remarkable diversity in inflorescence architecture, and pedicel length is one of the key contributors to this diversity. In Arabidopsis thaliana, the receptor-like kinase ERECTA (ER) mediated signaling pathway plays important roles in regulating inflorescence architecture by promoting cell proliferation. However, the regulating mechanism remains elusive in the pedicel. Genetic interactions between ERECTA signaling and the chromatin remodeling complex SWR1 in the control of inflorescence architecture were studied...
March 13, 2017: New Phytologist
https://www.readbyqxmd.com/read/28288875/the-histone-h2a-isoform-hist2h2ac-is-a-novel-regulator-of-proliferation-and-epithelial-mesenchymal-transition-in-mammary-epithelial-and-in-breast-cancer-cells
#7
Fátima Liliana Monteiro, Rui Vitorino, Jun Wang, Hugo Cardoso, Hugo Laranjeira, Joana Simões, Margarida Caldas, Rui Henrique, Francisco Amado, Cecilia Williams, Carmen Jerónimo, Luisa A Helguero
Proliferation and differentiation are controlled through chromatin remodelling. Therefore, there is an enormous biological significance and clinical value in understanding how specific signalling pathways are affected by histone replacement in the nucleosome. In this work, mass spectrometry was used to screen HC11 mammary epithelial cells for changes in histone levels throughout cell differentiation. The canonical histone isoform Histone H2A type 2-C (Hist2h2ac) was found only in undifferentiated/proliferating cells...
March 10, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28284059/reactivating-p53-and-inducing-tumor-apoptosis-rita-enhances-the-response-of-rita-sensitive-colorectal-cancer-cells-to-chemotherapeutic-agents-5-fluorouracil-and-oxaliplatin
#8
Armin Wiegering, Niels Matthes, Bettina Mühling, Monika Koospal, Anne Quenzer, Stephanie Peter, Christoph-Thomas Germer, Michael Linnebacher, Christoph Otto
Colorectal carcinoma (CRC) is the most common cancer of the gastrointestinal tract with frequently dysregulated intracellular signaling pathways, including p53 signaling. The mainstay of chemotherapy treatment of CRC is 5-fluorouracil (5FU) and oxaliplatin. The two anticancer drugs mediate their therapeutic effect via DNA damage-triggered signaling. The small molecule reactivating p53 and inducing tumor apoptosis (RITA) is described as an activator of wild-type and reactivator of mutant p53 function, resulting in elevated levels of p53 protein, cell growth arrest, and cell death...
March 8, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28270613/smn-deficiency-in-severe-models-of-spinal-muscular-atrophy-causes-widespread-intron-retention-and-dna-damage
#9
Mohini Jangi, Christina Fleet, Patrick Cullen, Shipra V Gupta, Shila Mekhoubad, Eric Chiao, Norm Allaire, C Frank Bennett, Frank Rigo, Adrian R Krainer, Jessica A Hurt, John P Carulli, John F Staropoli
Spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease, is the leading monogenic cause of infant mortality. Homozygous loss of the gene survival of motor neuron 1 (SMN1) causes the selective degeneration of lower motor neurons and subsequent atrophy of proximal skeletal muscles. The SMN1 protein product, survival of motor neuron (SMN), is ubiquitously expressed and is a key factor in the assembly of the core splicing machinery. The molecular mechanisms by which disruption of the broad functions of SMN leads to neurodegeneration remain unclear...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28258158/dual-role-of-the-histone-variant-h2a-z-in-transcriptional-regulation-of-stress-response-genes
#10
Weronika Sura, Michał Kabza, Wojciech M Karlowski, Tomasz Bieluszewski, Marta Kuś-Slowinska, Łukasz Pawełoszek, Jan Sadowski, Piotr A Ziolkowski
The influence of the histone variant H2A.Z on transcription remains a long-standing conundrum. Here, by analyzing the actin-related protein6 mutant, which is impaired in H2A.Z deposition, and by H2A.Z profiling in stress conditions, we investigated the impact of this histone variant on gene expression in Arabidopsis thaliana. We demonstrate that the arp6 mutant exhibits anomalies in response to osmotic stress. Indeed, stress-responsive genes are overrepresented amongst those hyperactive in arp6. In wild-type plants, these genes exhibit high levels of H2A...
March 3, 2017: Plant Cell
https://www.readbyqxmd.com/read/28257702/gene-resistance-to-transcriptional-reprogramming-following-nuclear-transfer-is-directly-mediated-by-multiple-chromatin-repressive-pathways
#11
Jerome Jullien, Munender Vodnala, Vincent Pasque, Mami Oikawa, Kei Miyamoto, George Allen, Sarah Anne David, Vincent Brochard, Stan Wang, Charles Bradshaw, Haruhiko Koseki, Vittorio Sartorelli, Nathalie Beaujean, John Gurdon
Understanding the mechanism of resistance of genes to reactivation will help improve the success of nuclear reprogramming. Using mouse embryonic fibroblast nuclei with normal or reduced DNA methylation in combination with chromatin modifiers able to erase H3K9me3, H3K27me3, and H2AK119ub1 from transplanted nuclei, we reveal the basis for resistance of genes to transcriptional reprogramming by oocyte factors. A majority of genes is affected by more than one type of treatment, suggesting that resistance can require repression through multiple epigenetic mechanisms...
March 2, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28254622/molecular-analyses-on-neospora-caninum-triggered-netosis-in-the-caprine-system
#12
R Villagra-Blanco, L M R Silva, U Gärtner, H Wagner, K Failing, A Wehrend, A Taubert, C Hermosilla
Neospora caninum is an obligate intracellular protozoan parasite causing serious reproductive disorders in large and small ruminants worldwide. Polymorphonuclear neutrophils (PMN) react against multiple invading pathogens through different mechanisms including the release of neutrophil extracellular traps (NETs). Here, in vitro interactions of caprine PMN and N. caninum tachyzoites were studied. Scanning electron microscopic- and immunofluorescence-analyses demonstrated that caprine PMN undergo NETosis upon contact with tachyzoites of N...
February 28, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28242625/zmym3-regulates-brca1-localization-at-damaged-chromatin-to-promote-dna-repair
#13
Justin W C Leung, Nodar Makharashvili, Poonam Agarwal, Li-Ya Chiu, Renaud Pourpre, Michael B Cammarata, Joe R Cannon, Alana Sherker, Daniel Durocher, Jennifer S Brodbelt, Tanya T Paull, Kyle M Miller
Chromatin connects DNA damage response factors to sites of damaged DNA to promote the signaling and repair of DNA lesions. The histone H2A variants H2AX, H2AZ, and macroH2A represent key chromatin constituents that facilitate DNA repair. Through proteomic screening of these variants, we identified ZMYM3 (zinc finger, myeloproliferative, and mental retardation-type 3) as a chromatin-interacting protein that promotes DNA repair by homologous recombination (HR). ZMYM3 is recruited to DNA double-strand breaks through bivalent interactions with both histone and DNA components of the nucleosome...
February 27, 2017: Genes & Development
https://www.readbyqxmd.com/read/28242611/the-role-of-variant-histone-h2av-in-d-melanogaster-larval-hematopoiesis
#14
Melina Grigorian, Heather DeBruhl, Joseph S Lipsick
Replication-independent histone variants can replace the canonical replication-dependent histones. Vertebrates have multiple H2A variant histones, including H2AZ and H2AX that are present in most eukaryotes. H2AZ regulates transcriptional activation as well as maintenance of gene silencing, while H2AX is important in DNA damage repair. The fruit fly Drosophila melanogaster has only one histone H2A variant (H2AV), which is a chimera of H2AZ and H2AX. In this study we found that lack of H2AV led to the formation of black melanotic masses in the third instar larvae of Drosophila...
February 27, 2017: Development
https://www.readbyqxmd.com/read/28240985/a-palb2-interacting-domain-in-rnf168-couples-homologous-recombination-to-dna-break-induced-chromatin-ubiquitylation
#15
Martijn S Luijsterburg, Dimitris Typas, Marie-Christine Caron, Wouter W Wiegant, Diana van den Heuvel, Rick A Boonen, Anthony M Couturier, Leon H Mullenders, Jean-Yves Masson, Haico van Attikum
DNA double-strand breaks (DSB) elicit a ubiquitylation cascade that controls DNA repair pathway choice. This cascade involves the ubiquitylation of histone H2A by the RNF168 ligase and the subsequent recruitment of RIF1, which suppresses homologous recombination (HR) in G1 cells. The RIF1-dependent suppression is relieved in S/G2 cells, allowing PALB2-driven HR to occur. With the inhibitory impact of RIF1 relieved, it remains unclear how RNF168-induced ubiquitylation influences HR. Here, we uncover that RNF168 links the HR machinery to H2A ubiquitylation in S/G2 cells...
February 27, 2017: ELife
https://www.readbyqxmd.com/read/28235947/human-centromeric-cenp-a-chromatin-is-a-homotypic-octameric-nucleosome-at-all-cell-cycle-points
#16
Yael Nechemia-Arbely, Daniele Fachinetti, Karen H Miga, Nikolina Sekulic, Gautam V Soni, Dong Hyun Kim, Adeline K Wong, Ah Young Lee, Kristen Nguyen, Cees Dekker, Bing Ren, Ben E Black, Don W Cleveland
Chromatin assembled with centromere protein A (CENP-A) is the epigenetic mark of centromere identity. Using new reference models, we now identify sites of CENP-A and histone H3.1 binding within the megabase, α-satellite repeat-containing centromeres of 23 human chromosomes. The overwhelming majority (97%) of α-satellite DNA is found to be assembled with histone H3.1-containing nucleosomes with wrapped DNA termini. In both G1 and G2 cell cycle phases, the 2-4% of α-satellite assembled with CENP-A protects DNA lengths centered on 133 bp, consistent with octameric nucleosomes with DNA unwrapping at entry and exit...
March 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28228717/mild-hypothermia-attenuates-the-anesthetic-isoflurane-induced-cytotoxicity
#17
Cheng Li, Yuanlin Dong, Dan Chen, Zhongcong Xie, Yiying Zhang
The commonly used inhalation anesthetic isoflurane has been reported to induce DNA damage and cytotoxicity. However, the methods to attenuate these effects remain largely to be determined. Mild hypothermia has neuroprotective effects. We therefore set out to assess whether mild hypothermia could protect the isoflurane-induced DNA damage and cytotoxicity. Moreover, we investigated the underlying mechanisms by assessing the effects of mild hypothermia on the isoflurane-induced changes in ATP levels. H4 human neuroglioma cells were treated with 2% isoflurane for 3 or 6 h with and without mild hypothermia (35°C)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28223110/h2a-and-ca-l-hipposin-gene-characteristic-analysis-and-expression-responses-to-aeromonas-hydrophila-infection-in-carassius-aurutus
#18
Xianghui Kong, Xiangmin Wu, Chao Pei, Jie Zhang, Xianliang Zhao, Li Li, Guoxing Nie, Xuejun Li
Antimicrobial peptide is an important component of the host innate immune system and thus serves a crucial function in host defense against microbial invasion. In this study, H2A and derived antimicrobial peptide Ca-L-hipposin were cloned and characterized in Carassius aurutus. The gene H2A full-length cDNA is 908 bp and includes a 5'-terminal untranslated region (UTR) of 55 bp and a 3'-terminal UTR of 466 bp with a canonical polyadenylation signal sequence AATAA, as well as an open reading frame (ORF) of 387 bp encoding a polypeptide of 128 amino acids, with a molecular weight of 13...
February 20, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28213359/methylation-of-the-phosphatase-transcription-activator-eya1-by-protein-arginine-methyltransferase-1-mechanistic-functional-and-structural-studies
#19
Xingguo Li, Allison Eberhardt, Jeanne N Hansen, Dirk Bohmann, Haitao Li, Nina F Schor
The eyes absent (EYA) family proteins are conserved transcriptional coactivators with intrinsic protein phosphatase activity. They play an essential role in the development of various organs in metazoans. These functions are associated with a unique combination of phosphatase and transactivation activities. However, it remains poorly understood how these activities and the consequent biologic functions of EYA are regulated. Here, we demonstrate that 2 conserved arginine residues, R304 and R306, of EYA1 are essential for its in vitro phosphatase activity and in vivo function during Drosophila eye development...
February 17, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28185200/automated-high-content-screening-of-%C3%AE-h2ax-expression-in-hela-cells
#20
Nate Hopp, Jodi Hagen, Birte Aggeler, Alexander E Kalyuzhny
Due to their inherent nature, DNA strands can be easily broken by various environmental factors including chemical agents and ionizing radiation. Unrepaired DNA double-stranded breaks (DSBs) may result in genetic instability and have a strong negative impact on the integrity of the genome. It has been found that DSBs are always followed by phosphorylation of histone protein H2AX, a member of the H2A family, and immunocytochemical detection of phosphorylated H2AX (referred to as γ-H2AX) is one of the frequently used techniques for assessing DNA damage...
2017: Methods in Molecular Biology
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