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Z-DNA binding protein

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https://www.readbyqxmd.com/read/28069948/genomic-targeting-of-epigenetic-probes-using-a-chemically-tailored-cas9-system
#1
Glen P Liszczak, Zachary Z Brown, Samuel H Kim, Rob C Oslund, Yael David, Tom W Muir
Recent advances in the field of programmable DNA-binding proteins have led to the development of facile methods for genomic localization of genetically encodable entities. Despite the extensive utility of these tools, locus-specific delivery of synthetic molecules remains limited by a lack of adequate technologies. Here we combine the flexibility of chemical synthesis with the specificity of a programmable DNA-binding protein by using protein trans-splicing to ligate synthetic elements to a nuclease-deficient Cas9 (dCas9) in vitro and subsequently deliver the dCas9 cargo to live cells...
January 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28027977/cleidocranial-dysplasia-clinical-endocrinologic-and-molecular-findings-in-15-patients-from-11-families
#2
Firdevs Dinçsoy Bir, Nuriye Dinçkan, Yeliz Güven, Firdevs Baş, Umut Altunoğlu, Senem S Kuvvetli, Şükran Poyrazoğlu, Güven Toksoy, Hülya Kayserili, Z Oya Uyguner
Cleidocranial dysplasia (CCD) is an autosomal dominant disorder characterized by skeletal anomalies such as delayed closure of the cranial sutures, underdeveloped or absent clavicles, multiple dental abnormalities, short stature and osteoporosis. RUNX2, encoding Runt DNA-binding domain protein important in osteoblast differentiation, is the only known gene related to the disease and identified as responsible in 70% of the cases. Our clinical evaluations revealed that short stature present at a rate of 28.6%, osteoporosis at a rate of 57...
December 24, 2016: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/27978938/-mechanism-of-action-of-the-sirt1-foxo1-adipor2-signaling-pathway-in-alcoholic-fatty-liver-disease
#3
Z Sun, J Y Zhou
Long-term alcohol stimulation may inhibit the expression of silent information regulator 1 in hepatocytes, which increases the acetylation level of forkhead box transcription factor O1, reduces nuclear localization, and reduces the binding capacity of DNA sequence. This further downregulates the expression of downstream adiponectin receptor 2 and microsomal triglyceride transfer protein, causes lipid metabolism disorders and triglyceride deposition in hepatocytes by affecting adiponectin signal transduction and synthesis of very-low-density lipoprotein, and finally promotes the development of alcoholic fatty liver disease...
November 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27929803/an-autopsy-verified-case-of-ftld-tdp-type-a-with-upper-motor-neuron-predominant-motor-neuron-disease-mimicking-mm2-thalamic-type-sporadic-creutzfeldt-jakob-disease
#4
Yuichi Hayashi, Yasushi Iwasaki, Akira Takekoshi, Nobuaki Yoshikura, Takahiko Asano, Maya Mimuro, Akio Kimura, Katsuya Satoh, Tetsuyuki Kitamoto, Mari Yoshida, Takashi Inuzuka
Here we report an autopsy-verified case of frontotemporal lobar degeneration (FTLD)-transactivation responsive region (TAR) DNA binding protein (TDP) type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD). A 69-year-old woman presented with an 11-month history of progressive dementia, irritability, insomnia, and gait disturbance without a family history of dementia or prion disease. Neurological examination revealed severe dementia, frontal signs, and exaggerated bilateral tendon reflexes...
November 2016: Prion
https://www.readbyqxmd.com/read/27917412/zbp1-dai-is-an-innate-sensor-of-influenza-virus-triggering-the-nlrp3-inflammasome-and-programmed-cell-death-pathways
#5
Teneema Kuriakose, Si Ming Man, R K Subbarao Malireddi, Rajendra Karki, Sannula Kesavardhana, David E Place, Geoffrey Neale, Peter Vogel, Thirumala-Devi Kanneganti
The interferon-inducible protein Z-DNA binding protein 1 (ZBP1, also known as DNA-dependent activator of IFN-regulatory factors (DAI) and DLM-1) was identified as a dsDNA sensor, which instigates innate immune responses. However, this classification has been disputed and whether ZBP1 functions as a pathogen sensor during an infection has remained unknown. Herein, we demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the RIPK1-RIPK3-Caspase-8 axis...
August 5, 2016: Science Immunology
https://www.readbyqxmd.com/read/27893714/the-lim-protein-ajuba-promotes-colorectal-cancer-cell-survival-through-suppression-of-jak1-stat1-ifit2-network
#6
H Jia, L Song, Q Cong, J Wang, H Xu, Y Chu, Q Li, Y Zhang, X Zou, C Zhang, Y E Chin, X Zhang, Z Li, K Zhu, B Wang, H Peng, Z Hou
The LIM protein AJUBA is a scaffold protein participating in the regulation of cell adhesion, mitosis, DNA damage, cell differentiation, proliferation, migration and gene transcription. However, its roles in tumorigenesis and progression are poorly defined. Here, we report that AJUBA is highly expressed in colorectal cancer (CRC) and promotes CRC cell growth in culture and in xenografted mice via an inhibition of apoptosis. AJUBA represses the expression of IFIT2 gene, an interferon-stimulated gene and a known apoptosis inducer and tumour suppressor to mediate its resistance to apoptosis...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27856245/nmr-elucidation-of-reduced-b-z-transition-activity-of-pkz-protein-kinase-at-high-nacl-concentration
#7
Ae-Ree Lee, Yeo-Jin Seo, Seo-Ree Choi, Kyoung-Seok Ryu, Hae-Kap Cheong, Shim Sung Lee, Masato Katahira, Chin-Ju Park, Joon-Hwa Lee
A Z-DNA binding protein (ZBP)-containing protein kinase (PKZ) in fish species has an important role in the innate immune response. Previous structural studies of the Zα domain of the PKZ from Carassius auratus (caZαPKZ) showed that the protein initially binds to B-DNA and induces B-Z transition of double stranded DNA in a salt concentration-dependent manner. However, the significantly reduced B-Z transition activity of caZαPKZ at high salt concentration was not fully understood. In this study, we present the binding affinity of the protein for B-DNA and Z-DNA and characterize its extremely low B-Z transition activity at 250 mM NaCl...
January 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27826836/enzymology-of-mammalian-dna-methyltransferases
#8
Renata Z Jurkowska, Albert Jeltsch
DNA methylation is currently one of the hottest topics in basic and biomedical research. Despite tremendous progress in understanding the structures and biochemical properties of the mammalian DNA nucleotide methyltransferases (DNMTs), principles of their regulation in cells have only begun to be uncovered. In mammals, DNA methylation is introduced by the DNMT1, DNMT3A, and DNMT3B enzymes, which are all large multi-domain proteins. These enzymes contain a catalytic C-terminal domain with a characteristic cytosine-C5 methyltransferase fold and an N-terminal part with different domains that interacts with other proteins and chromatin and is involved in targeting and regulation of the DNMTs...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27825659/ferritin-1-silencing-effect-in-rhipicephalus-sanguineus-sensu-lato-acari-ixodidae-during-experimental-infection-with-ehrlichia-canis
#9
Joana Ferrolho, Sandra Antunes, Gustavo S Sanches, Joana Couto, Patrícia M Évora, Catarina Rosa, Marcos R André, Rosângela Z Machado, Gervásio H Bechara, Ana Domingos
Rhipicephalus sanguineus sensu lato (s.l.) is a very common ectoparasite of domestic dogs able to transmit several pathogens of human and veterinary importance. Tick infestations and tick-borne diseases (TBDs) remain a serious and persistent problem, due to the lack of efficient control measures. It is therefore vital that novel approaches to control are pursued. Whilst vaccination is recognised as a potential control method to reduce tick infestation, no anti-R. sanguineus vaccine is available. Ticks depend on their blood meals to obtain nutrients and to achieve sexual maturity, which exposes them to vast amounts of iron...
January 2017: Ticks and Tick-borne Diseases
https://www.readbyqxmd.com/read/27819682/ripk1-inhibits-zbp1-driven-necroptosis-during-development
#10
Kim Newton, Katherine E Wickliffe, Allie Maltzman, Debra L Dugger, Andreas Strasser, Victoria C Pham, Jennie R Lill, Merone Roose-Girma, Søren Warming, Margaret Solon, Hai Ngu, Joshua D Webster, Vishva M Dixit
Receptor-interacting protein kinase 1 (RIPK1) promotes cell survival-mice lacking RIPK1 die perinatally, exhibiting aberrant caspase-8-dependent apoptosis and mixed lineage kinase-like (MLKL)-dependent necroptosis. However, mice expressing catalytically inactive RIPK1 are viable, and an ill-defined pro-survival function for the RIPK1 scaffold has therefore been proposed. Here we show that the RIP homotypic interaction motif (RHIM) in RIPK1 prevents the RHIM-containing adaptor protein ZBP1 (Z-DNA binding protein 1; also known as DAI or DLM1) from activating RIPK3 upstream of MLKL...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27819681/ripk1-counteracts-zbp1-mediated-necroptosis-to-inhibit-inflammation
#11
Juan Lin, Snehlata Kumari, Chun Kim, Trieu-My Van, Laurens Wachsmuth, Apostolos Polykratis, Manolis Pasparakis
Receptor-interacting protein kinase 1 (RIPK1) regulates cell death and inflammation through kinase-dependent and -independent functions. RIPK1 kinase activity induces caspase-8-dependent apoptosis and RIPK3 and mixed lineage kinase like (MLKL)-dependent necroptosis. In addition, RIPK1 inhibits apoptosis and necroptosis through kinase-independent functions, which are important for late embryonic development and the prevention of inflammation in epithelial barriers. The mechanism by which RIPK1 counteracts RIPK3-MLKL-mediated necroptosis has remained unknown...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27818052/scaffolds-for-oriented-and-close-packed-immobilization-of-immunoglobulins
#12
REVIEW
Masumi Iijima, Shun'ichi Kuroda
Immunosensing is a widely used technique that detects the interactions between antibodies and antigens such as biochemical markers, pathogens, allergens, and tumor-associated antigens. Since target antigens are often of high molecular mass and their binding affinities are sometimes weak, the spatial arrangement of immunoglobulin Gs (IgGs) on immunosensing probes should be optimized by presenting them in as close-packed a manner as possible and reducing steric hindrance around the antigen-binding Fv regions...
March 15, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/27813331/sliding-on-dna-from-peptides-to-small-molecules
#13
Kan Xiong, Graham S Erwin, Aseem Z Ansari, Paul C Blainey
Many DNA binding proteins utilize one-dimensional (1D) diffusion along DNA to accelerate their DNA target recognition. Although 1D diffusion of proteins along DNA has been studied for decades, a quantitative understanding is only beginning to emerge and few chemical tools are available to apply 1D diffusion as a design principle. Recently, we discovered that peptides can bind and slide along DNA-even transporting cargo along DNA. Such molecules are known as molecular sleds. Here, to advance our understanding of structure-function relationships governing sequence nonspecific DNA interaction of natural molecular sleds and to explore the potential for controlling sliding activity, we test the DNA binding and sliding activities of chemically modified peptides and analogs, and show that synthetic small molecules can slide on DNA...
November 21, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27802172/interplay-between-sox7-and-runx1-regulates-hemogenic-endothelial-fate-in-the-yolk-sac
#14
Andrew J Lilly, Guilherme Costa, Anne Largeot, Muhammad Z H Fadlullah, Michael Lie-A-Ling, Georges Lacaud, Valerie Kouskoff
Endothelial to hematopoietic transition (EHT) is a dynamic process involving the shutting down of endothelial gene expression and switching on of hematopoietic gene transcription. Although the factors regulating EHT in hemogenic endothelium (HE) of the dorsal aorta have been relatively well studied, the molecular regulation of yolk sac HE remains poorly understood. Here, we show that SOX7 inhibits the expression of RUNX1 target genes in HE, while having no effect on RUNX1 expression itself. We establish that SOX7 directly interacts with RUNX1 and inhibits its transcriptional activity...
December 1, 2016: Development
https://www.readbyqxmd.com/read/27797380/dna-demethylation-induces-sall4-gene-re-expression-in-subgroups-of-hepatocellular-carcinoma-associated-with-hepatitis-b-or-c-virus-infection
#15
H Fan, Z Cui, H Zhang, S K Mani, A Diab, L Lefrancois, N Fares, P Merle, O Andrisani
Sal-like protein 4 (SALL4), an embryonic stem cell transcriptional regulator, is re-expressed by an unknown mechanism in poor prognosis hepatocellular carcinoma (HCC), often associated with chronic hepatitis B virus (HBV) infection. Herein, we investigated the mechanism of SALL4 re-expression in HBV-related HCCs. We performed bisulfite sequencing PCR of genomic DNA isolated from HBV-related HCCs and HBV replicating cells, and examined DNA methylation of a CpG island located downstream from SALL4 transcriptional start site (TSS)...
October 31, 2016: Oncogene
https://www.readbyqxmd.com/read/27785392/epigenetic-alterations-in-patients-with-type-2-diabetes-mellitus
#16
S Karachanak-Yankova, R Dimova, D Nikolova, D Nesheva, M Koprinarova, S Maslyankov, R Tafradjiska, P Gateva, M Velizarova, Z Hammoudeh, N Stoynev, D Toncheva, T Tankova, I Dimova
Epigenetic changes, in particular DNA methylation processes, play a role in the pathogenesis and progression of type 2 diabetes mellitus (T2DM) linking genetic and environmental factors. To clarify this role, we have analyzed in patients with different duration of T2DM: (i) expression levels of methyl-CpG-binding domain protein 2 (MBD2) as marker of DNA methylation, and ii) methylation changes in 22 genes connected to cellular stress and toxicity. We have analyzed MBD2 mRNA expression levels in16 patients and 12 controls and the methylation status of stress and toxicity genes in four DNA pools: (i) controls; (ii) newly-diagnosed T2DM patients; (iii) patients with T2DM duration of <5 years and (iv) of >5 years...
December 1, 2015: Balkan Journal of Medical Genetics: BJMG
https://www.readbyqxmd.com/read/27770267/2-aryl-benzimidazole-conjugate-induced-apoptosis-in-human-breast-cancer-mcf-7-cells-through-caspase-independent-pathway
#17
V Lakshma Nayak, Narayana Nagesh, A Ravikumar, Chandrakant Bagul, M V P S Vishnuvardhan, Vunnam Srinivasulu, Ahmed Kamal
Apoptosis is a representative form of programmed cell death, which has been assumed to be critical for cancer prevention. Thus, any agent that can induce apoptosis may be useful for cancer treatment and apoptosis induction is arguably the most potent defense against cancer promotion. In our previous studies, 2-aryl benzimidazole conjugates were synthesized and evaluated for their antiproliferative activity and one of the new molecule (2f) was considered as a potential lead. This lead molecule showed significant antiproliferative activity against human breast cancer cell line, MCF-7...
October 21, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27730230/an-evolution-based-dna-binding-residue-predictor-using-a-dynamic-query-driven-learning-scheme
#18
H Chai, J Zhang, G Yang, Z Ma
DNA-binding proteins play a pivotal role in various biological activities. Identification of DNA-binding residues (DBRs) is of great importance for understanding the mechanism of gene regulations and chromatin remodeling. Most traditional computational methods usually construct their predictors on static non-redundant datasets. They excluded many homologous DNA-binding proteins so as to guarantee the generalization capability of their models. However, those ignored samples may potentially provide useful clues when studying protein-DNA interactions, which have not obtained enough attention...
October 12, 2016: Molecular BioSystems
https://www.readbyqxmd.com/read/27667278/-effect-of-notch1-2-3-genes-silencing-on-notch-and-nuclear-factor-%C3%AE%C2%BAb-signaling-pathway-of-macrophages-derived-from-patients-with-coronary-artery-disease
#19
Z B Ruan, X L Fu, W Li, J Ye, R Z Wang, Y G Yin, L Zhu
Objective: To investigate the effects of Notch1, 2, 3 genes silencing by siRNA on Notch signaling pathway (Delta-like 4(DLL4), Jagged 1(JAG1)) and nuclear factor-κB (NF-κB) signaling pathway (IκBα, P52) of macrophages derived from patients with coronary artery disease (CAD), thus to explore the potential genetic treatment perspectives for CAD. Methods: Peripheral blood mononuclear cells of CAD patients were isolated by density gradient centrifugation and transformed by phorbol-12-myristate-13-acetate (PMA) to macrophages...
September 24, 2016: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/27658575/differential-dna-methylation-of-the-meiosis-specific-gene-fkbp6-in-testes-of-yak-and-cattle-yak-hybrids
#20
B Li, H Luo, Q Weng, S Wang, Z Pan, Z Xie, W Wu, H Liu, Q Li
FK506-binding protein 6 (FKBP6) is essential for meiosis during mammalian spermatogenesis. However, the molecular regulation of FKBP6 during spermatogenesis remains unclear. In the present study, we performed molecular characterization of the meiosis-specific gene FKBP6 in yak testes. Yak FKBP6 encodes a polypeptide of 295 amino acid residues with an FK506-binding domain (FKBP_C) and three tetratricopeptide repeat domains. The methylation level of the FKBP6 promoter in testes was significantly higher in cattle-yak with male sterility than in yak, and the FKBP6 promoter was methylated in liver tissues in which FKBP6 is not expressed...
December 2016: Reproduction in Domestic Animals, Zuchthygiene
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