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https://www.readbyqxmd.com/read/29166597/mammalian-hp1-isoforms-have-specific-roles-in-heterochromatin-structure-and-organization
#1
Laia Bosch-Presegué, Helena Raurell-Vila, Joshua K Thackray, Jessica González, Carmen Casal, Noriko Kane-Goldsmith, Miguel Vizoso, Jeremy P Brown, Antonio Gómez, Juan Ausió, Timo Zimmermann, Manel Esteller, Gunnar Schotta, Prim B Singh, Lourdes Serrano, Alejandro Vaquero
HP1 is a structural component of heterochromatin. Mammalian HP1 isoforms HP1α, HP1β, and HP1γ play different roles in genome stability, but their precise role in heterochromatin structure is unclear. Analysis of Hp1α(-/-), Hp1β(-/-), and Hp1γ(-/-) MEFs show that HP1 proteins have both redundant and unique functions within pericentric heterochromatin (PCH) and also act globally throughout the genome. HP1α confines H4K20me3 and H3K27me3 to regions within PCH, while its absence results in a global hyper-compaction of chromatin associated with a specific pattern of mitotic defects...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29151149/impact-of-xist-rna-on-chromatin-modifications-and-transcriptional-silencing-maintenance-at-different-stages-of-imprinted-x-chromosome-inactivation-in-vole-microtus-levis
#2
Alexander I Shevchenko, Elena V Grigor'eva, Sergey P Medvedev, Irina S Zakharova, Elena V Dementyeva, Eugeny A Elisaphenko, Anastasia A Malakhova, Sophia V Pavlova, Suren M Zakian
In vole Microtus levis, cells of preimplantation embryo and extraembryonic tissues undergo imprinted X chromosome inactivation (iXCI) which is triggered by a long non-coding nuclear RNA, Xist. At early stages of iXCI, chromatin of vole inactive X chromosome is enriched with the HP1 heterochromatin-specific protein, trimethylated H3K9 and H4K20 attributable to constitutive heterochromatin. In the study, using vole trophoblast stem (TS) cells as a model of iXCI, we further investigated chromatin of the inactive X chromosome of M...
November 18, 2017: Chromosoma
https://www.readbyqxmd.com/read/29126440/chromatin-organization-changes-during-the-establishment-and-maintenance-of-the-postmitotic-state
#3
Yiqin Ma, Laura Buttitta
BACKGROUND: Genome organization changes during development as cells differentiate. Chromatin motion becomes increasingly constrained and heterochromatin clusters as cells become restricted in their developmental potential. These changes coincide with slowing of the cell cycle, which can also influence chromatin organization and dynamics. Terminal differentiation is often coupled with permanent exit from the cell cycle, and existing data suggest a close relationship between a repressive chromatin structure and silencing of the cell cycle in postmitotic cells...
November 10, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29124886/cbx3-heterochromatin-protein-1-gamma-is-significantly-upregulated-in-patients-with-non-small-cell-lung-cancer
#4
Shih-Chieh Chang, Yi-Chun Lai, Yen-Chung Chen, Nai-Kuan Wang, Wei-Shu Wang, Jiun-I Lai
AIM: Lung cancer is typically categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC comprises of the majority of lung cancer with a poor prognosis in advanced cases. Transcriptional profiling studies, including microarrays and RNA-sequencing studies, have significantly enriched our knowledge of gene expression patterns in NSCLC. A recent transcriptional profiling study identified high prevalence of CBX3/HP1-gamma upregulation in human NSCLC samples...
November 10, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29111699/investigation-of-trimethyllysine-binding-by-the-hp1-chromodomain-via-unnatural-amino-acid-mutagenesis
#5
Stefanie A Baril, Amber L Koenig, Mackenzie W Krone, Katherine I Albanese, Cyndi Qixin He, Ga Young Lee, Kendall N Houk, Marcey L Waters, Eric M Brustad
Trimethyllysine (Kme3) reader proteins are targets for inhibition due to their role in mediating gene expression. Although all such reader proteins bind Kme3 in an aromatic cage, the driving force for binding may differ; some readers exhibit evidence for cation-π interactions whereas others do not. We report a general unnatural amino acid mutagenesis approach to quantify the contribution of individual tyrosines to cation binding using the HP1 chromodomain as a model system. We demonstrate that two tyrosines (Y24 and Y48) bind to a Kme3-histone tail peptide via cation-π interactions, but linear free energy trends suggest they do not contribute equally to binding...
November 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29109320/effects-of-the-ratio-between-pigment-and-bleaching-gel-on-the-fracture-resistance-and-dentin-microhardness-of-endodontically-treated-teeth
#6
Marina Og Galloza, Keren Cf Jordão-Basso, Matheus C Bandeca, Samuel O Costa, Alvaro H Borges, Mateus R Tonetto, Fabio C Tirintan, Kátia C Keine, Milton C Kuga
INTRODUCTION: The aim of this study was to evaluate the effects of bleaching gel using 35% hydrogen peroxide (HP), associated with red carmine pigment (RC), in the 3:1 or 1:1 ratio, on fracture resistance and dentin microhardness of endodontically treated teeth. MATERIALS AND METHODS: A total of 40 lower incisors were endodontically treated and divided into four groups (n = 10), according to the bleaching protocol: G1 (HP3), 35% HP + RC (3:1); G2 (HP1), 35% HP + RC (1:1); G3 (positive), 38% HP; and G4 (negative), unbleached...
November 1, 2017: Journal of Contemporary Dental Practice
https://www.readbyqxmd.com/read/29104730/haptoglobin-genotype-and-outcome-after-subarachnoid-haemorrhage-new-insights-from-a-meta-analysis
#7
Ben Gaastra, James Glazier, Diederik Bulters, Ian Galea
Haptoglobin (Hp) is a plasma protein involved in clearing extracellular haemoglobin and regulating inflammation; it exists as two genetic variants (Hp1 and Hp2). In a meta-analysis of six published studies, we confirm that Hp genotype affects short-term outcome (cerebral vasospasm and/or delayed cerebral ischemia) after subarachnoid haemorrhage (SAH) but not long-term outcome (Glasgow Outcome Score and modified Rankin Scale between one and three months). A closer examination of the heterozygous group revealed that the short-term outcome of Hp2-1 individuals clustered with that of Hp1-1 and not Hp2-2, suggesting that the presence of one Hp1 allele was sufficient to confer protection...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29101771/modifications-at-k31-on-the-lateral-surface-of-histone-h4-contribute-to-genome-structure-and-expression-in-apicomplexan-parasites
#8
Fabien Sindikubwabo, Shuai Ding, Tahir Hussain, Philippe Ortet, Mohamed Barakat, Sebastian Baumgarten, Dominique Cannella, Andrés Palencia, Alexandre Bougdour, Lucid Belmudes, Yohann Couté, Isabelle Tardieux, Cyrille Y Botté, Artur Scherf, Mohamed-Ali Hakimi
An unusual genome architecture characterizes the two related human parasitic pathogens Plasmodium falciparum and Toxoplasma gondii. A major fraction of the bulk parasite genome is packaged as transcriptionally permissive euchromatin with few loci embedded in silenced heterochromatin. Primary chromatin shapers include histone modifications at the nucleosome lateral surface close to the DNA but their mode of action remains unclear. We now identify versatile modifications at Lys31 within the globular domain of histone H4 that crucially determine genome organization and expression in Apicomplexa parasites...
November 4, 2017: ELife
https://www.readbyqxmd.com/read/29078403/induction-of-h3k9me3-and-dna-methylation-by-tethered-heterochromatin-factors-in-neurospora-crassa
#9
Jordan D Gessaman, Eric U Selker
Functionally different chromatin domains display distinct chemical marks. Constitutive heterochromatin is commonly associated with trimethylation of lysine 9 on histone H3 (H3K9me3), hypoacetylated histones, and DNA methylation, but the contributions of and interplay among these features are not fully understood. To dissect the establishment of heterochromatin, we investigated the relationships among these features using an in vivo tethering system in Neurospora crassa Artificial recruitment of the H3K9 methyltransferase DIM-5 (defective in methylation-5) induced H3K9me3 and DNA methylation at a normally active, euchromatic locus but did not bypass the requirement of DIM-7, previously implicated in the localization of DIM-5, indicating additional DIM-7 functionality...
November 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28985346/single-molecule-kinetic-analysis-of-hp1-chromatin-binding-reveals-a-dynamic-network-of-histone-modification-and-dna-interactions
#10
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...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28977666/chd3-and-chd4-form-distinct-nurd-complexes-with-different-yet-overlapping-functionality
#11
Helen Hoffmeister, Andreas Fuchs, Fabian Erdel, Sophia Pinz, Regina Gröbner-Ferreira, Astrid Bruckmann, Rainer Deutzmann, Uwe Schwartz, Rodrigo Maldonado, Claudia Huber, Anne-Sarah Dendorfer, Karsten Rippe, Gernot Längst
CHD3 and CHD4 (Chromodomain Helicase DNA binding protein), two highly similar representatives of the Mi-2 subfamily of SF2 helicases, are coexpressed in many cell lines and tissues and have been reported to act as the motor subunit of the NuRD complex (nucleosome remodeling and deacetylase activities). Besides CHD proteins, NuRD contains several repressors like HDAC1/2, MTA2/3 and MBD2/3, arguing for a role as a transcriptional repressor. However, the subunit composition varies among cell- and tissue types and physiological conditions...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28963472/zfp296-negatively-regulates-h3k9-methylation-in-embryonic-development-as-a-component-of-heterochromatin
#12
Takumi Matsuura, Satsuki Miyazaki, Tatsushi Miyazaki, Fumi Tashiro, Jun-Ichi Miyazaki
The Cys2/His2-type zinc finger protein Zfp296 has been implicated in stem cell pluripotency and tumor pathogenesis. However, its mechanisms remain elusive. Here, we demonstrated that a Zfp296 deficiency in mice impairs germ-cell development and embryonic growth. Zfp296 was intracellularly localized to heterochromatin in embryos. A GST-Zfp296 pull-down experiment using ES cell nuclear extract followed by LC-MS/MS showed that Zfp296 interacts with component proteins of heterochromatin (such as HP1, Dnmt1, Dnmt3b, and ATRX) and the NuRD complex...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28960920/a-proteo-genomic-analysis-of-haptoglobin-in-malaria
#13
Gauri Awasthi, Suchi Tyagi, Vipin Kumar, Sandip Kumar Patel, Dharmendar Rojh, Vijeth Sakrappanavar, Sanjay Kumar Kochar, Arunansu Talukdar, Biaus Samanta, Aparup Das, Sanjeeva Srivastava, Swati Patankar
Haptoglobin (Hp), an acute phase inflammatory protein has been associated with malaria pathogenesis in several proteomics studies. The gene has two co-dominant alleles: Hp1 and Hp2 that produce three genotypes: Hp1/Hp1, Hp1/Hp2 and Hp2/Hp2. In this study, we perform validation of the proteomics data with Multiple Reaction Monitoring Mass Spectroscopy (MRM-MS). We further analyze the association of the Hp gene variants with severe, non-severe malaria and community (healthy) controls using genotyping PCRs and DNA sequencing...
September 27, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/28942425/chromosome-healing-is-promoted-by-the-telomere-cap-component-hiphop-in-drosophila
#14
Rebeccah L Kurzhals, Laura Fanti, A C Gonzalez Ebsen, Yikang S Rong, Sergio Pimpinelli, Kent G Golic
The addition of a new telomere onto a chromosome break, a process termed healing, has been studied extensively in organisms that utilize telomerase to maintain their telomeres. In comparison, relatively little is known about how new telomeres are constructed on broken chromosomes in organisms that do not use telomerase. Chromosome healing was studied in somatic and germline cells of Drosophila melanogaster, a nontelomerase species. We observed, for the first time, that broken chromosomes can be healed in somatic cells...
November 2017: Genetics
https://www.readbyqxmd.com/read/28942089/biochemical-basis-for-distinct-roles-of-the-heterochromatin-proteins-swi6-and-chp2
#15
R Stefan Isaac, Serena Sanulli, Ryan Tibble, Michael Hornsby, Matthew Ravalin, Charles S Craik, John D Gross, Geeta J Narlikar
Heterochromatin protein 1 (HP1) family proteins are conserved chromatin binding proteins involved in gene silencing, chromosome packaging, and chromosome segregation. These proteins recognize histone H3 lysine 9 methylated tails via their chromodomain and recruit additional ligand proteins with diverse activities through their dimerization domain, the chromoshadow domain. Species that have HP1 proteins possess multiple paralogs that perform non-overlapping roles in vivo. How different HP1 proteins, which are highly conserved, perform different functions is not well understood...
November 24, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28916764/rapid-and-reversible-epigenome-editing-by-endogenous-chromatin-regulators
#16
Simon M G Braun, Jacob G Kirkland, Emma J Chory, Dylan Husmann, Joseph P Calarco, Gerald R Crabtree
Understanding the causal link between epigenetic marks and gene regulation remains a central question in chromatin biology. To edit the epigenome we developed the FIRE-Cas9 system for rapid and reversible recruitment of endogenous chromatin regulators to specific genomic loci. We enhanced the dCas9-MS2 anchor for genome targeting with Fkbp/Frb dimerizing fusion proteins to allow chemical-induced proximity of a desired chromatin regulator. We find that mSWI/SNF (BAF) complex recruitment is sufficient to oppose Polycomb within minutes, leading to activation of bivalent gene transcription in mouse embryonic stem cells...
September 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28900795/haptoglobin-levels-but-not-hp1-hp2-polymorphism-are-associated-with-polycystic-ovary-syndrome
#17
Laura M L Carvalho, Cláudia N Ferreira, Daisy K D de Oliveira, Kathryna F Rodrigues, Rita C F Duarte, Márcia F A Teixeira, Luana B Xavier, Ana Lúcia Candido, Fernando M Reis, Ieda F O Silva, Fernanda M F Campos, Karina B Gomes
PURPOSE: Proteomic studies suggest an association between haptoglobin (Hp) and polycystic ovary syndrome (PCOS). Hp is a classic inflammatory marker and binds to the intravascular hemoglobin, avoiding the oxidative damages that can be caused by free hemoglobin. Inflammation and oxidative stress are important in the pathogenesis of the PCOS, one of the most frequent metabolic diseases in women. METHODS: To validate these proteomic studies, we developed a controlled cross-sectional study that aimed to evaluate the Hp levels and allelic and genotypic frequencies of Hp1-Hp2 polymorphism in Brazilian women with PCOS...
September 13, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28886332/evolving-models-of-heterochromatin-from-foci-to-liquid-droplets
#18
Antonis Tatarakis, Reza Behrouzi, Danesh Moazed
Two recent papers (Larson et al., 2017; Strom et al., 2017) in Nature propose that heterochromatic domains are organized into phase-separated liquid compartments. Here we highlight the main findings that support the liquid-like nature of HP1 domains and discuss their functional implications in gene silencing and genome organization.
September 7, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28881656/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#19
Georgios Pongas, Marianne K Kim, Dong J Min, Carrie D House, Elizabeth Jordan, Natasha Caplen, Sirisha Chakka, Joyce Ohiri, Michael J Kruhlak, Christina M Annunziata
Ovarian cancer (OC) is a heterogeneous disease characterized by defective DNA repair. Very few targets are universally expressed in the high grade serous (HGS) subtype. We previously identified that CHK1 was overexpressed in most of HGSOC. Here, we sought to understand the DNA damage response (DDR) to CHK1 inhibition and increase the anti-tumor activity of this pathway. We found BRD4 suppression either by siRNA or BRD4 inhibitor JQ1 enhanced the cytotoxicity of CHK1 inhibition. Interestingly, BRD4 was amplified and/or upregulated in a subset of HGSOC with statistical correlation to overall survival...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28855512/atrx-is-a-regulator-of-therapy-induced-senescence-in-human-cells
#20
Marta Kovatcheva, Will Liao, Mary E Klein, Nicolas Robine, Heather Geiger, Aimee M Crago, Mark A Dickson, William D Tap, Samuel Singer, Andrew Koff
Senescence is a state of stable cell cycle exit with important implications for development and disease. Here, we demonstrate that the chromatin remodeling enzyme ATRX is required for therapy-induced senescence. ATRX accumulates in nuclear foci and is required for therapy-induced senescence in multiple types of transformed cells exposed to either DNA damaging agents or CDK4 inhibitors. Mobilization into foci depends on the ability of ATRX to interact with H3K9me3 histone and HP1. Foci form soon after cells exit the cell cycle, before other hallmarks of senescence appear...
August 30, 2017: Nature Communications
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