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https://www.readbyqxmd.com/read/29035535/report-and-application-of-a-tool-compound-dataset
#1
Kyle V Butler, Ian A MacDonald, Nathaniel A Hathaway, Jian Jin
Small molecule tool compounds have enabled profound advances in life science research. These chemicals are potent, cell active, and selective, and thus, are suitable for interrogating biological processes. For these chemicals to be useful they must be correctly characterized and researchers must be aware of them. We mined the ChEMBL bioactivity database to identify high quality tool compounds in an unbiased way. We identified 407 best-in-class compounds for 278 protein targets, and these are reported in an annotated dataset...
October 16, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29033129/genome-nuclear-lamina-interactions-regulate-cardiac-stem-cell-lineage-restriction
#2
Andrey Poleshko, Parisha P Shah, Mudit Gupta, Apoorva Babu, Michael P Morley, Lauren J Manderfield, Jamie L Ifkovits, Damelys Calderon, Haig Aghajanian, Javier E Sierra-Pagán, Zheng Sun, Qiaohong Wang, Li Li, Nicole C Dubois, Edward E Morrisey, Mitchell A Lazar, Cheryl L Smith, Jonathan A Epstein, Rajan Jain
Progenitor cells differentiate into specialized cell types through coordinated expression of lineage-specific genes and modification of complex chromatin configurations. We demonstrate that a histone deacetylase (Hdac3) organizes heterochromatin at the nuclear lamina during cardiac progenitor lineage restriction. Specification of cardiomyocytes is associated with reorganization of peripheral heterochromatin, and independent of deacetylase activity, Hdac3 tethers peripheral heterochromatin containing lineage-relevant genes to the nuclear lamina...
October 7, 2017: Cell
https://www.readbyqxmd.com/read/29032247/specifications-of-targeting-heterochromatin-modifications-in-plants
#3
REVIEW
Jered M Wendte, Robert J Schmitz
Plants encode a diverse repertoire of DNA methyltransferases that have specialized to target cytosines for methylation in specific sequence contexts. These include the de novo methyltransferase, DOMAINS REARRANGED METHYLTRANSFERASE 2 (DRM2), which methylates cytosines in all sequence contexts through an RNA guided process, the CHROMOMETHYLASES (CMTs), which methylate CHH and CHG cytosines (where H is A, T, or C), and the maintenance methyltransferase, METHYLTRANSFERASE 1 (MET1), which maintains methylation of symmetrical CG contexts...
October 12, 2017: Molecular Plant
https://www.readbyqxmd.com/read/29030848/profiling-open-chromatin-structure-in-the%C3%A2-ovarian-somatic-cells-using-atac-seq
#4
Kensaku Murano, Yuka W Iwasaki, Haruhiko Siomi
The assay for transposase-accessible chromatin using sequencing (ATAC-seq) was recently established as a method to profile open chromatin, which overcomes the sample size limitations of the alternative methods DNase/MNase-seq. To investigate the role of Piwi in heterochromatin formation around transposable element loci, we have used ATAC-seq to examine chromatin accessibility at target transposable elements in a Drosophila cultured cell line, ovarian somatic cells (OSCs). In this chapter, we describe our method to profile open chromatin structure in OSCs using ATAC-seq...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29030538/proteasomes-beyond-proteolysis-roles-in-heterochromatin-maintenance
#5
Blaine Bartholomew
In addition to its proteolytic roles, the 26S proteasome is involved in regulating transcription and in promoting sites of active chromatin. In this report, Seo et al. provide evidence that the non-proteolytic 19S subunit of the 26S proteasome also regulates the spreading of inactive chromatin referred to as heterochromatin, suggesting further non-canonical roles of the proteasome in gene expression.
October 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29021213/whats-hows-and-whys-of-programmed-dna-elimination-in-tetrahymena
#6
REVIEW
Tomoko Noto, Kazufumi Mochizuki
Programmed genome rearrangements in ciliates provide fascinating examples of flexible epigenetic genome regulations and important insights into the interaction between transposable elements (TEs) and host genomes. DNA elimination in Tetrahymena thermophila removes approximately 12 000 internal eliminated sequences (IESs), which correspond to one-third of the genome, when the somatic macronucleus (MAC) differentiates from the germline micronucleus (MIC). More than half of the IESs, many of which show high similarity to TEs, are targeted for elimination in cis by the small RNA-mediated genome comparison of the MIC to the MAC...
October 2017: Open Biology
https://www.readbyqxmd.com/read/29020631/covalent-modifications-of-histone-h3k9-promote-binding-of-chd3
#7
Adam H Tencer, Khan L Cox, Luo Di, Joseph B Bridgers, Jie Lyu, Xiaodong Wang, Jennifer K Sims, Tyler M Weaver, Hillary F Allen, Yi Zhang, Jovylyn Gatchalian, Michael A Darcy, Matthew D Gibson, Jinzen Ikebe, Wei Li, Paul A Wade, Jeffrey J Hayes, Brian D Strahl, Hidetoshi Kono, Michael G Poirier, Catherine A Musselman, Tatiana G Kutateladze
Chromatin remodeling is required for genome function and is facilitated by ATP-dependent complexes, such as nucleosome remodeling and deacetylase (NuRD). Among its core components is the chromodomain helicase DNA binding protein 3 (CHD3) whose functional significance is not well established. Here, we show that CHD3 co-localizes with the other NuRD subunits, including HDAC1, near the H3K9ac-enriched promoters of the NuRD target genes. The tandem PHD fingers of CHD3 bind histone H3 tails and posttranslational modifications that increase hydrophobicity of H3K9-methylation or acetylation (H3K9me3 or H3K9ac)-enhance this interaction...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/29018479/epigenetic-regulation-of-cellular-senescence-and-aging
#8
REVIEW
Corinne Sidler, Olga Kovalchuk, Igor Kovalchuk
Aging is characterized by functional decline of diverse organs and an increased risk for several diseases. Therefore, a high interest exists in understanding the molecular mechanisms that stimulate aging at all levels, from cells and tissues to organs and organisms, in order to develop ways to promote healthy aging. While many molecular and biochemical mechanisms are already understood in some detail, the role of changes in epigenetic regulation has only begun to be considered in recent years. The age-dependent global reduction in heterochromatin, along with site-specific changes in the patterns of DNA methylation and modification of histones, have been observed in several aging model systems...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28992616/ns1-of-h7n9-influenza-a-virus-induces-no-mediated-cellular-senescence-in-neuro2a-cells
#9
Yinxia Yan, Yongming Du, Huali Zheng, Gefei Wang, Rui Li, Jieling Chen, Kangsheng Li
BACKGROUND/AIMS: The novel avian H7N9 influenza A virus has been detected in brain tissues and associated with central nervous system (CNS) symptoms in infected human and mice. Roles of its virulence factor, NS1 protein in influenza virus infected neuron has yet to be explored. METHODS: Nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in H7N9/NS1-expressed Neuro2a cells were detected by Griess test and western blotting. Cell proliferation rate of H7N9/NS1-expressing cells was recorded by Cell Counting Kit-8...
October 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28992061/glp-inhibits-heterochromatin-clustering-and-myogenic-differentiation-by-repressing-mecp2
#10
Min Hee Choi, Monica Palanichamy Kala, Jin Rong Ow, Vinay Kumar Rao, Sudha Suriyamurthy, Reshma Taneja
Myogenic differentiation is accompanied by alterations in the chromatin states, which permit or restrict the transcriptional machinery and thus impact distinctive gene expression profiles. The mechanisms by which higher-order chromatin remodeling is associated with gene activation and silencing during differentiation is not fully understood. In this study, we provide evidence that the euchromatic lysine methyltransferase GLP regulates heterochromatin organization and myogenic differentiation. Interestingly, GLP represses expression of the methyl-binding protein MeCP2 that induces heterochromatin clustering during differentiation...
August 23, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28991910/loss-of-xist-rna-from-the-inactive-x-during-b-cell-development-is-restored-in-a-dynamic-yy1-dependent-two-step-process-in-activated-b-cells
#11
Camille M Syrett, Vishal Sindhava, Suchita Hodawadekar, Arpita Myles, Guanxiang Liang, Yue Zhang, Satabdi Nandi, Michael Cancro, Michael Atchison, Montserrat C Anguera
X-chromosome inactivation (XCI) in female lymphocytes is uniquely regulated, as the inactive X (Xi) chromosome lacks localized Xist RNA and heterochromatin modifications. Epigenetic profiling reveals that Xist RNA is lost from the Xi at the pro-B cell stage and that additional heterochromatic modifications are gradually lost during B cell development. Activation of mature B cells restores Xist RNA and heterochromatin to the Xi in a dynamic two-step process that differs in timing and pattern, depending on the method of B cell stimulation...
October 9, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28991226/lsd1-promotes-s-phase-entry-and-tumorigenesis-via-chromatin-co-occupation-with-e2f1-and-selective-h3k9-demethylation
#12
Y He, Y Zhao, L Wang, L R Bohrer, Y Pan, L Wang, H Huang
Histone H3 lysine-9 (H3K9) methylation is essential for retinoblastoma protein (RB)-mediated heterochromatin formation, epigenetic silencing of S-phase genes and permanent cell cycle arrest or cellular senescence. Besides as an H3K4 demethylase, lysine-specific demethylase-1 (LSD1) has been shown to promote H3K9 demethylation. However, it is unexplored whether LSD1 has a causal role in regulating cell cycle entry and senescence. Here we demonstrate that genetic depletion or pharmacological inhibition of LSD1 triggers G1 arrest and cellular senescence...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28985346/single-molecule-kinetic-analysis-of-hp1-chromatin-binding-reveals-a-dynamic-network-of-histone-modification-and-dna-interactions
#13
Louise C Bryan, Daniel R Weilandt, Andreas L Bachmann, Sinan Kilic, Carolin C Lechner, Pascal D Odermatt, Georg E Fantner, Sandrine Georgeon, Oliver Hantschel, Vassily Hatzimanikatis, Beat Fierz
Chromatin recruitment of effector proteins involved in gene regulation depends on multivalent interaction with histone post-translational modifications (PTMs) and structural features of the chromatin fiber. Due to the complex interactions involved, it is currently not understood how effectors dynamically sample the chromatin landscape. Here, we dissect the dynamic chromatin interactions of a family of multivalent effectors, heterochromatin protein 1 (HP1) proteins, using single-molecule fluorescence imaging and computational modeling...
August 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28985345/replication-stress-induced-endogenous-dna-damage-drives-cellular-senescence-induced-by-a-sub-lethal-oxidative-stress
#14
Gireedhar Venkatachalam, Uttam Surana, Marie-Véronique Clément
Although oxidative stress has been shown to induce senescence and replication stress independently, no study has implicated unresolved replication stress as the driver for cellular senescence in response to oxidative stress. Using cells exposed to increasing concentrations of hydrogen peroxide, we show that sub-lethal amount of exogenous hydrogen peroxide induces two waves of DNA damage. The first wave is rapid and transient while the second wave coincides with the cells transition from the S to the G2/M phases of cell cycle...
July 31, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28981863/subtelomeres-constitute-a-safeguard-for-gene-expression-and-chromosome-homeostasis
#15
Sanki Tashiro, Yuki Nishihara, Kazuto Kugou, Kunihiro Ohta, Junko Kanoh
The subtelomere, a telomere-adjacent chromosomal domain, contains species-specific homologous DNA sequences, in addition to various genes. However, the functions of subtelomeres, particularly subtelomeric homologous (SH) sequences, remain elusive. Here, we report the first comprehensive analyses of the cellular functions of SH sequences in the fission yeast, Schizosaccharomyces pombe. Complete removal of SH sequences from the genome revealed that they are dispensable for mitosis, meiosis and telomere length control...
September 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28981559/description-of-the-karyotypes-of-stejneger-s-beaked-whale-mesoplodon-stejnegeri-and-hubbs-beaked-whale-m-carlhubbsi
#16
Nozomi Kurihara, Yuko Tajima, Tadasu K Yamada, Ayaka Matsuda, Takashi Matsuishi
The genus Mesoplodon (Cetacea: Odontoceti: Ziphiidae) is one of the few cetacean genera with the karyotype 2n = 42. The 2n = 42 karyotype of M. europaeus and M. carlhubbsi is largely consistent with the general cetacean karyotype 2n = 44, although other 2n = 42 karyotypes do not exhibit clear homologies with the general cetacean karyotype. Therefore, the chromosomes of Mesoplodon species may be the key to understanding cetacean karyological evolution. In the present study, the male karyotypes of M. stejnegeri and M...
October 2, 2017: Genetics and Molecular Biology
https://www.readbyqxmd.com/read/28980937/correction-a-team-of-heterochromatin-factors-collaborates-with-small-rna-pathways-to-combat-repetitive-elements-and-germline-stress
#17
Alicia N McMurchy, Przemyslaw Stempor, Tessa Gaarenstroom, Brian Wysolmerski, Yan Dong, Darya Aussianikava, Alex Appert, Ni Huang, Paulina Kolasinska-Zwierz, Alexandra Sapetschnig, Eric A Miska, Julie Ahringer
No abstract text is available yet for this article.
October 5, 2017: ELife
https://www.readbyqxmd.com/read/28977643/regulation-of-mitotic-recombination-between-dna-repeats-in-centromeres
#18
Faria Zafar, Akiko K Okita, Atsushi T Onaka, Jie Su, Yasuhiro Katahira, Jun-Ichi Nakayama, Tatsuro S Takahashi, Hisao Masukata, Takuro Nakagawa
Centromeres that are essential for faithful segregation of chromosomes consist of unique DNA repeats in many eukaryotes. Although recombination is under-represented around centromeres during meiosis, little is known about recombination between centromere repeats in mitotic cells. Here, we compared spontaneous recombination that occurs between ade6B/ade6X inverted repeats integrated at centromere 1 (cen1) or at a non-centromeric ura4 locus in fission yeast. Remarkably, distinct mechanisms of homologous recombination (HR) were observed in centromere and non-centromere regions...
August 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28977426/histone-h1-depletion-triggers-an-interferon-response-in-cancer-cells-via-activation-of-heterochromatic-repeats
#19
Andrea Izquierdo-Bouldstridge, Alberto Bustillos, Carles Bonet-Costa, Patricia Aribau-Miralbés, Daniel García-Gomis, Marc Dabad, Anna Esteve-Codina, Laura Pascual-Reguant, Sandra Peiró, Manel Esteller, Matthew Murtha, Lluís Millán-Ariño, Albert Jordan
Histone H1 has seven variants in human somatic cells and contributes to chromatin compaction and transcriptional regulation. Knock-down (KD) of each H1 variant in breast cancer cells results in altered gene expression and proliferation differently in a variant specific manner with H1.2 and H1.4 KDs being most deleterious. Here we show combined depletion of H1.2 and H1.4 has a strong deleterious effect resulting in a strong interferon (IFN) response, as evidenced by an up-regulation of many IFN-stimulated genes (ISGs) not seen in individual nor in other combinations of H1 variant KDs...
August 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28975734/a-jack-of-all-trades-the-rna-binding-protein-vigilin
#20
REVIEW
Matthew Hk Cheng, Ralf-Peter Jansen
The vigilin family of proteins is evolutionarily conserved from yeast to humans and characterized by the proteins' 14 or 15 hnRNP K homology (KH) domains, typically associated with RNA-binding. Vigilin is the largest RNA-binding protein (RBP) in the KH domain-containing family and one of the largest RBP known to date. Since its identification 30 years ago, vigilin has been shown to bind over 700 mRNAs and has been associated with cancer progression and cardiovascular disease. We provide a brief historic overview of vigilin research and outline the proteins' different functions, focusing on maintenance of genome ploidy, heterochromatin formation, RNA export, as well as regulation of translation, mRNA transport, and mRNA stability...
October 4, 2017: Wiley Interdisciplinary Reviews. RNA
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