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https://www.readbyqxmd.com/read/28525753/the-u6-snrna-m-6-a-methyltransferase-mettl16-regulates-sam-synthetase-intron-retention
#1
Kathryn E Pendleton, Beibei Chen, Kuanqing Liu, Olga V Hunter, Yang Xie, Benjamin P Tu, Nicholas K Conrad
Maintenance of proper levels of the methyl donor S-adenosylmethionine (SAM) is critical for a wide variety of biological processes. We demonstrate that the N(6)-adenosine methyltransferase METTL16 regulates expression of human MAT2A, which encodes the SAM synthetase expressed in most cells. Upon SAM depletion by methionine starvation, cells induce MAT2A expression by enhanced splicing of a retained intron. Induction requires METTL16 and its methylation substrate, a vertebrate conserved hairpin (hp1) in the MAT2A 3' UTR...
May 18, 2017: Cell
https://www.readbyqxmd.com/read/28514126/-haptoglobin-polymorphism-as-an-independent-predictor-of-diabetic-nephropathy-and-retinopathy
#2
Inbal Dahan, Nadia Thauho, Farid Nakhoul, Nakhoul Nakhoul, Hanin Jabaly, Evgeny Farber
The antioxidant protein haptoglobin (Hp) plays a major role in the development of diabetic complications such as diabetic nephropathy and retinopathy. In humans, two alleles of Hp were identified: 1 and 2 with three possible genotypes: 1-1, 2-1, and 2-2. The Hp protein products differ in their biochemical and biophysical properties, such as their antioxidant capacity. The Hp1 protein is superior to the Hp2 protein in binding to free hemoglobin and neutralizing its oxidative potential and the accompanying renal and retinal injury...
July 2016: Harefuah
https://www.readbyqxmd.com/read/28487337/haptoglobin-hp2-variant-promotes-premature-cardiovascular-death-in-stroke-survivors
#3
Petra Ijäs, Susanna Melkas, Jani Saksi, Antti Jula, Matti Jauhiainen, Niku Oksala, Tarja Pohjasvaara, Markku Kaste, Pekka J Karhunen, Perttu Lindsberg, Timo Erkinjuntti
BACKGROUND AND PURPOSE: Haptoglobin (Hp) is an acute phase plasma protein protecting tissues from oxidative damage. It exists in 2 variant alleles (hp1/hp2) giving rise to 3 protein isoforms with different biochemical properties and efficiency to limit oxidative stress. We previously found that hp2 variant is associated with stroke risk in the patients with carotid stenosis and the risk of ischemic cardiovascular events in a general population cohort. This study examined the hypothesis that Hp genotype is associated with general cardiovascular risk in patients with stroke...
May 9, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28483815/drosophila-dalmatian-combines-sororin-and-shugoshin-roles-in-establishment-and-protection-of-cohesion
#4
Takashi Yamada, Eri Tahara, Mai Kanke, Keiko Kuwata, Tomoko Nishiyama
Sister chromatid cohesion is crucial to ensure chromosome bi-orientation and equal chromosome segregation. Cohesin removal via mitotic kinases and Wapl has to be prevented in pericentromeric regions in order to protect cohesion until metaphase, but the mechanisms of mitotic cohesion protection remain elusive in Drosophila Here, we show that dalmatian (Dmt), an ortholog of the vertebrate cohesin-associated protein sororin, is required for protection of mitotic cohesion in flies. Dmt is essential for cohesion establishment during interphase and is enriched on pericentromeric heterochromatin...
May 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28459455/dna-sequence-homology-induces-cytosine-to-thymine-mutation-by-a-heterochromatin-related-pathway-in-neurospora
#5
Eugene Gladyshev, Nancy Kleckner
Most eukaryotic genomes contain substantial amounts of repetitive DNA organized in the form of constitutive heterochromatin and associated with repressive epigenetic modifications, such as H3K9me3 and C5 cytosine methylation (5mC). In the fungus Neurospora crassa, H3K9me3 and 5mC are catalyzed, respectively, by a conserved SUV39 histone methyltransferase, DIM-5, and a DNMT1-like cytosine methyltransferase, DIM-2. Here we show that DIM-2 can also mediate repeat-induced point mutation (RIP) of repetitive DNA in N...
May 1, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28416369/plasma-levels-of-apolipoprotein-a1-and-lecithin-cholesterol-acyltransferase-in-type-2-diabetes-mellitus-correlations-with-haptoglobin-phenotypes
#6
Samir Awadallah, Mohammed Madkour, Reem Al Hamidi, Esraa Abo Alwafa, Maram Hattab, Buhour Zakkour, Amna Al-Matroushi, Eslah Ahmed, Mariam Al-Kitbi
BACKGROUND: Previous studies have demonstrated that hemoglobin-haptoglobin (Hb-Hp) complex plays a role in developing vascular complications in type 2 diabetes mellitus (T2DM). The complexes bind with Apolipoprotein A1 (ApoA1) of high-density lipoprotein (HDL), affecting the function of Lecithin:Cholesterol Acyltransferase (LCAT), and impairing the reverse cholesterol transport mechanism (RCT). This study investigated the influence of Hp phenotypes on serum levels of ApoA1 and LCAT in patients with T2DM...
April 7, 2017: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/28398513/a-rare-splice-donor-mutation-in-the-haptoglobin-gene-associates-with-blood-lipid-levels-and-coronary-artery-disease
#7
Eythor Bjornsson, Hannes Helgason, Gisli Halldorsson, Anna Helgadottir, Arnaldur Gylfason, Birte Kehr, Adalbjorg Jonasdottir, Aslaug Jonasdottir, Asgeir Sigurdsson, Asmundur Oddsson, Gudmar Thorleifsson, Olafur Th Magnusson, Solveig Gretarsdottir, Florian Zink, Ragnar P Kristjansson, Margret Asgeirsdottir, Dorine W Swinkels, Lambertus A Kiemeney, Gudmundur I Eyjolfsson, Olof Sigurdardottir, Gisli Masson, Isleifur Olafsson, Gudmundur Thorgeirsson, Hilma Holm, Unnur Thorsteinsdottir, Daniel F Gudbjartsson, Patrick Sulem, Kari Stefansson
Common sequence variants at the haptoglobin gene (HP) have been associated with lipid levels. Through whole-genome sequencing of 8,453 Icelanders, we discovered a splice donor founder mutation in HP (NM_001126102.1:c.190 + 1G > C, minor allele frequency = 0.56%). This mutation occurs on the HP1 allele of the common copy number variant in HP and leads to a loss of function of HP1. It associates with lower levels of haptoglobin (P = 2.1 × 10-54), higher levels of non-high density lipoprotein cholesterol (β = 0...
April 7, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28392109/compartmentalization-of-dna-damage-response-between-heterochromatin-and-euchromatin-is-mediated-by-distinct-h2a-histone-variants
#8
Zdravko J Lorković, Chulmin Park, Malgorzata Goiser, Danhua Jiang, Marie-Therese Kurzbauer, Peter Schlögelhofer, Frédéric Berger
DNA double-strand break (DSB) repair depends on the ataxia telangiectasia mutated (ATM) kinase that phosphorylates the conserved C-terminal SQ motif present in the histone variant H2A.X [1-7]. In constitutive heterochromatin of mammals, DSB repair is delayed and relies on phosphorylation of the proteins HP1 and KAP1 by ATM [2, 8-14]. However, KAP1 is not conserved in plants and the HP1-related protein Like-HP1 (LHP1) is not localized at constitutive heterochromatin [15], suggesting that in plants, alternative mechanisms could be responsible for repair of DSBs in heterochromatin...
April 24, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28385889/substituted-cysteine-accessibility-method-scam-analysis-of-the-transport-domain-of-human-concentrative-nucleoside-transporter-3-hcnt3-and-other-family-members-reveals-features-of-structural-and-functional-importance
#9
Ras Mulinta, Sylvia Y M Yao, Amy M L Ng, Carol E Cass, James D Young
The human SLC28 family of concentrative nucleoside transporter (CNT) proteins has three members, hCNT1, hCNT2 and hCNT3. Na+-coupled hCNT1 and hCNT2 transport pyrimidine and purine nucleosides, respectively, whereas hCNT3 transports both pyrimidine and purine nucleosides utilizing Na+ and/or H+ electrochemical gradients. Escherichia coli CNT family member NupC resembles hCNT1 in permeant selectivity but is H+-coupled. Using heterologous expression in Xenopus oocytes and the engineered cysteine-less hCNT3 protein hCNT3(C-), substituted cysteine accessibility method (SCAM) analysis with the membrane-impermeant thiol reactive reagent p-chloromercuribenzene sulfonate (PCMBS) was performed on the transport domain (IH2, HP1, TM7, TM8), as well as TM9 of the scaffold domain of the protein...
April 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28370635/precision-aliphatic-polyesters-with-alternating-microstructures-via-cross-metathesis-polymerization-an-event-of-sequence-control
#10
Zi-Long Li, Fu-Rong Zeng, Ji-Mei Ma, Lin-Hao Sun, Zhen Zeng, Hong Jiang
Sequence-regulated polymerization is realized upon sequential cross-metathesis polymerization (CMP) and exhaustive hydrogenation to afford precision aliphatic polyesters with alternating sequences. This strategy is particularly suitable for the arrangement of well-known monomer units including glycolic acid, lactic acid, and caprolactic acid on polymer chain in a predetermined sequence. First of all, structurally asymmetric monomers bearing acrylate and α-olefin terminuses are generated in an efficient and straightforward fashion...
April 3, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/28369503/populus-simonii-%C3%A3-populus-nigra-wrky70-is-involved-in-salt-stress-and-leaf-blight-disease-responses
#11
Hui Zhao, Jing Jiang, Kailong Li, Guifeng Liu, Chung-Jui Tsai
WRKY transcription factors (TFs) are important regulators in the complex stress response signaling networks in plants, but the detailed mechanisms underlying these regulatory networks have not been fully characterized. In the present study, we identified a Group III WRKY gene (PsnWRKY70, Potri.016G137900) from Populussimonii × Populusnigra and explored its function under salt and pathogen stresses. The promoter sequence that is located 2471-bp upstream from the start codon (SC) of PsnWRKY70 contained many stress-responsive cis-elements...
March 22, 2017: Tree Physiology
https://www.readbyqxmd.com/read/28366787/manduca-sexta-hemolymph-protease-1-activated-by%C3%A2-an%C3%A2-unconventional-non-proteolytic-mechanism-mediates%C3%A2-immune%C3%A2-responses
#12
Yan He, Yang Wang, Fan Yang, Haobo Jiang
Tissue damage or pathogen invasion triggers the auto-proteolysis of an initiating serine protease (SP), rapidly leading to sequential cleavage activation of other cascade members to set off innate immune responses in insects. Recently, we presented evidence that Manduca sexta hemolymph protease-1 zymogen (proHP1) is a member of the SP system in this species, and may activate proHP6. HP6 stimulates melanization and induces antimicrobial peptide synthesis. Here we report that proHP1 adopts an active conformation (*) to carry out its function, without a requirement for proteolytic activation...
May 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28359954/comparison-of-the-effects-of-commercial-coated-and-uncoated-zno-nanomaterials-and-zn-compounds-in-kidney-bean-phaseolus-vulgaris-plants
#13
Illya A Medina-Velo, Ana C Barrios, Nubia Zuverza-Mena, Jose A Hernandez-Viezcas, Chong Hyun Chang, Zhaoxia Ji, Jeffrey I Zink, Jose R Peralta-Videa, Jorge L Gardea-Torresdey
Bean (Phaseolus vulgaris) plants were grown for 45 days in soil amended with either uncoated (Z-COTE(®)) and coated (Z-COTE HP1(®)) ZnO nanomaterials (NMs), bulk ZnO and ZnCl2, at 0-500mg/kg. At harvest, growth parameters, chlorophyll, and essential elements were determined. None of the treatments affected germination and pod production, and only ZnCl2 at 250 and 500mg/kg reduced relative chlorophyll content by 34% and 46%, respectively. While Z-COTE(®) did not produce phenotypic changes, Z-COTE HP1(®), at all concentrations, increased root length (∼44%) and leaf length (∼13%) compared with control...
March 6, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28346356/microinjection-of-antibodies-targeting-the-lamin-a-c-histone-binding-site-blocks-mitotic-entry-and-reveals-separate-chromatin-interactions-with-hp1-cenpb-and-pml
#14
Charles R Dixon, Melpomeni Platani, Alexandr A Makarov, Eric C Schirmer
Lamins form a scaffold lining the nucleus that binds chromatin and contributes to spatial genome organization; however, due to the many other functions of lamins, studies knocking out or altering the lamin polymer cannot clearly distinguish between direct and indirect effects. To overcome this obstacle, we specifically targeted the mapped histone-binding site of A/C lamins by microinjecting antibodies specific to this region predicting that this would make the genome more mobile. No increase in chromatin mobility was observed; however, interestingly, injected cells failed to go through mitosis, while control antibody-injected cells did...
March 25, 2017: Cells
https://www.readbyqxmd.com/read/28294943/a-team-of-heterochromatin-factors-collaborates-with-small-rna-pathways-to-combat-repetitive-elements-and-germline-stress
#15
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
Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28293301/histone-peptide-microarray-screen-of-chromo-and-tudor-domains-defines-new-histone-lysine-methylation-interactions
#16
Erin K Shanle, Stephen A Shinsky, Joseph B Bridgers, Narkhyun Bae, Cari Sagum, Krzysztof Krajewski, Scott B Rothbart, Mark T Bedford, Brian D Strahl
BACKGROUND: Histone posttranslational modifications (PTMs) function to regulate chromatin structure and function in part through the recruitment of effector proteins that harbor specialized "reader" domains. Despite efforts to elucidate reader domain-PTM interactions, the influence of neighboring PTMs and the target specificity of many reader domains is still unclear. The aim of this study was to use a high-throughput histone peptide microarray platform to interrogate 83 known and putative histone reader domains from the chromo and Tudor domain families to identify their interactions and characterize the influence of neighboring PTMs on these interactions...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28293300/silencing-markers-are-retained-on-pericentric-heterochromatin-during-murine-primordial-germ-cell-development
#17
Aristea Magaraki, Godfried van der Heijden, Esther Sleddens-Linkels, Leonidas Magarakis, Wiggert A van Cappellen, Antoine H F M Peters, Joost Gribnau, Willy M Baarends, Maureen Eijpe
BACKGROUND: In the nuclei of most mammalian cells, pericentric heterochromatin is characterized by DNA methylation, histone modifications such as H3K9me3 and H4K20me3, and specific binding proteins like heterochromatin-binding protein 1 isoforms (HP1 isoforms). Maintenance of this specialized chromatin structure is of great importance for genome integrity and for the controlled repression of the repetitive elements within the pericentric DNA sequence. Here we have studied histone modifications at pericentric heterochromatin during primordial germ cell (PGC) development using different fixation conditions and fluorescent immunohistochemical and immunocytochemical protocols...
2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/28287329/atg4b-contains-a-c-terminal-lir-motif-important-for-binding-and-efficient-cleavage-of-mammalian-orthologs-of-yeast-atg8
#18
Mads Skytte Rasmussen, Stéphane Mouilleron, Birendra Kumar Shrestha, Martina Wirth, Rebecca Lee, Kenneth Bowitz Larsen, Yakubu Abudu Princely, Nicola O'Reilly, Eva Sjøttem, Sharon A Tooze, Trond Lamark, Terje Johansen
The cysteine protease ATG4B cleaves off one or more C-terminal residues of the inactive proform of proteins of the ortholog and paralog LC3 and GABARAP subfamilies of yeast Atg8 to expose a C-terminal glycine that is conjugated to phosphatidylethanolamine during autophagosome formation. We show that ATG4B contains a C-terminal LC3-interacting region (LIR) motif important for efficient binding to and cleavage of LC3 and GABARAP proteins. We solved the crystal structures of the GABARAPL1-ATG4B C-terminal LIR complex...
February 15, 2017: Autophagy
https://www.readbyqxmd.com/read/28273462/negative-regulators-of-an-rnai-heterochromatin-positive-feedback-loop-safeguard-somatic-genome-integrity-in-tetrahymena
#19
Jan H Suhren, Tomoko Noto, Kensuke Kataoka, Shan Gao, Yifan Liu, Kazufumi Mochizuki
RNAi-mediated positive feedback loops are pivotal for the maintenance of heterochromatin, but how they are downregulated at heterochromatin-euchromatin borders is not well understood. In the ciliated protozoan Tetrahymena, heterochromatin is formed exclusively on the sequences that are removed from the somatic genome by programmed DNA elimination, and an RNAi-mediated feedback loop is important for assembling heterochromatin on the eliminated sequences. In this study, we show that the heterochromatin protein 1 (HP1)-like protein Coi6p, its interaction partners Coi7p and Lia5p, and the histone demethylase Jmj1p are crucial for confining the production of small RNAs and the formation of heterochromatin to the eliminated sequences...
March 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28236007/function-of-heterochromatin-protein-1-during-dna-repair
#20
REVIEW
Eva Bártová, Barbora Malyšková, Denisa Komůrková, Soňa Legartová, Jana Suchánková, Jana Krejčí, Stanislav Kozubek
This review focuses on the function of heterochromatin protein HP1 in response to DNA damage. We specifically outline the regulatory mechanisms in which HP1 and its interacting partners are involved. HP1 protein subtypes (HP1α, HP1β, and HP1γ) are the main components of constitutive heterochromatin, and HP1α and HP1β in particular are responsible for heterochromatin maintenance. The recruitment of these proteins to DNA lesions is also important from the perspective of proper DNA repair mechanisms. For example, HP1α is necessary for the binding of the main DNA damage-related protein 53BP1 at DNA repair foci, which are positive not only for the HP1α protein but also for the RAD51 protein, a component of DNA repair machinery...
May 2017: Protoplasma
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