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https://www.readbyqxmd.com/read/28636604/liquid-droplet-formation-by-hp1%C3%AE-suggests-a-role-for-phase-separation-in-heterochromatin
#1
Adam G Larson, Daniel Elnatan, Madeline M Keenen, Michael J Trnka, Jonathan B Johnston, Alma L Burlingame, David A Agard, Sy Redding, Geeta J Narlikar
Gene silencing by heterochromatin is proposed to occur in part as a result of the ability of heterochromatin protein 1 (HP1) proteins to spread across large regions of the genome, compact the underlying chromatin and recruit diverse ligands. Here we identify a new property of the human HP1α protein: the ability to form phase-separated droplets. While unmodified HP1α is soluble, either phosphorylation of its N-terminal extension or DNA binding promotes the formation of phase-separated droplets. Phosphorylation-driven phase separation can be promoted or reversed by specific HP1α ligands...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28636597/phase-separation-drives-heterochromatin-domain-formation
#2
Amy R Strom, Alexander V Emelyanov, Mustafa Mir, Dmitry V Fyodorov, Xavier Darzacq, Gary H Karpen
Constitutive heterochromatin is an important component of eukaryotic genomes that has essential roles in nuclear architecture, DNA repair and genome stability, and silencing of transposon and gene expression. Heterochromatin is highly enriched for repetitive sequences, and is defined epigenetically by methylation of histone H3 at lysine 9 and recruitment of its binding partner heterochromatin protein 1 (HP1). A prevalent view of heterochromatic silencing is that these and associated factors lead to chromatin compaction, resulting in steric exclusion of regulatory proteins such as RNA polymerase from the underlying DNA...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28622804/g-quadruplex-based-exo-iii-assisted-signal-amplification-aptasensor-for-the-colorimetric-detection-of-adenosine
#3
Lei Xu, Xin Shen, Bingzhi Li, Chunhong Zhu, Xuemin Zhou
Adenosine is an endogenous nucleotide pivotally involved in nucleic acid and energy metabolism. Its excessive existence may indicate tumorigenesis, typically lung cancer. Encouraged by its significance as the clinical biomarker, sensitive assay methods towards adenosine have been popularized, with high cost and tedious procedures as the inevitable defects. Herein, we report a label-free aptamer-based exonuclease III (Exo III) amplification colorimetric aptasensor for the highly sensitive and cost-effective detection of adenosine...
August 8, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/28587163/a-tox21-approach-to-altered-epigenetic-landscapes-assessing-epigenetic-toxicity-pathways-leading-to-altered-gene-expression-and-oncogenic-transformation-in-vitro
#4
REVIEW
Craig L Parfett, Daniel Desaulniers
An emerging vision for toxicity testing in the 21st century foresees in vitro assays assuming the leading role in testing for chemical hazards, including testing for carcinogenicity. Toxicity will be determined by monitoring key steps in functionally validated molecular pathways, using tests designed to reveal chemically-induced perturbations that lead to adverse phenotypic endpoints in cultured human cells. Risk assessments would subsequently be derived from the causal in vitro endpoints and concentration vs...
June 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28548929/brd4-facilitates-dna-damage-response-and-represses-cbx5-heterochromatin-protein-1-hp1
#5
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...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28525753/the-u6-snrna-m-6-a-methyltransferase-mettl16-regulates-sam-synthetase-intron-retention
#6
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
#7
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
#8
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
#9
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...
June 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28459455/dna-sequence-homology-induces-cytosine-to-thymine-mutation-by-a-heterochromatin-related-pathway-in-neurospora
#10
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...
June 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
#11
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
#12
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 blood 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...
June 15, 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
#13
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
#14
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 analysis with the membrane-impermeant thiol reactive reagent p-chloromercuribenzene sulfonate was performed on the transport domain (interfacial helix 2, hairpin 1, putative transmembrane domain (TM) 7, and TM8), as well as TM9 of the scaffold domain of the protein...
June 9, 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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