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Z-DNA binding protein

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https://www.readbyqxmd.com/read/29145618/the-histone-variant-h2a-z-promotes-initiation-of-meiotic-recombination-in-fission-yeast
#1
Shintaro Yamada, Kazuto Kugou, Da-Qiao Ding, Yurika Fujita, Yasushi Hiraoka, Hiroshi Murakami, Kunihiro Ohta, Takatomi Yamada
Meiotic recombination is initiated by programmed formation of DNA double strand breaks (DSBs), which are mainly formed at recombination hotspots. Meiotic DSBs require multiple proteins including the conserved protein Spo11 and its cofactors, and are influenced by chromatin structure. For example, local chromatin around hotspots directly impacts DSB formation. Moreover, DSB is proposed to occur in a higher-order chromatin architecture termed 'axis-loop', in which many loops protrude from cohesin-enriched axis...
November 14, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29073079/inhibition-of-dai-dependent-necroptosis-by-the-z-dna-binding-domain-of-the-vaccinia-virus-innate-immune-evasion-protein-e3
#2
Heather Koehler, Samantha Cotsmire, Jeffrey Langland, Karen V Kibler, Daniel Kalman, Jason W Upton, Edward S Mocarski, Bertram L Jacobs
Vaccinia virus (VACV) encodes an innate immune evasion protein, E3, which contains an N-terminal Z-nucleic acid binding (Zα) domain that is critical for pathogenicity in mice. Here we demonstrate that the N terminus of E3 is necessary to inhibit an IFN-primed virus-induced necroptosis. VACV deleted of the Zα domain of E3 (VACV-E3LΔ83N) induced rapid RIPK3-dependent cell death in IFN-treated L929 cells. Cell death was inhibited by the RIPK3 inhibitor, GSK872, and infection with this mutant virus led to phosphorylation and aggregation of MLKL, the executioner of necroptosis...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29058709/molecular-analysis-of-prc2-recruitment-to-dna-in-chromatin-and-its-inhibition-by-rna
#3
Xueyin Wang, Richard D Paucek, Anne R Gooding, Zachary Z Brown, Eva J Ge, Tom W Muir, Thomas R Cech
Many studies have revealed pathways of epigenetic gene silencing by Polycomb repressive complex 2 (PRC2) in vivo, but understanding the underlying molecular mechanisms requires biochemistry. Here we analyze interactions of reconstituted human PRC2 with nucleosome complexes. Histone modifications, the H3K27M cancer mutation, and inclusion of JARID2 or EZH1 in the PRC2 complex have unexpectedly minor effects on PRC2-nucleosome binding. Instead, protein-free linker DNA dominates the PRC2-nucleosome interaction...
October 23, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29058695/dna-methylation-signal-has-a-major-role-in-the-response-of-human-breast-cancer-cells-to-the-microenvironment
#4
P Mathot, M Grandin, G Devailly, F Souaze, V Cahais, S Moran, M Campone, Z Herceg, M Esteller, P Juin, P Mehlen, R Dante
Breast cancer-associated fibroblasts (CAFs) have a crucial role in tumor initiation, metastasis and therapeutic resistance by secreting various growth factors, cytokines, protease and extracellular matrix components. Soluble factors secreted by CAFs are involved in many pathways including inflammation, metabolism, proliferation and epigenetic modulation, suggesting that CAF-dependent reprograming of cancer cells affects a large set of genes. This paracrine signaling has an important role in tumor progression, thus deciphering some of these processes could lead to relevant discoveries with subsequent clinical implications...
October 23, 2017: Oncogenesis
https://www.readbyqxmd.com/read/29017946/cloning-and-expression-of-malabar-grouper-epinephelus-malabaricus-adar1-gene-in-response-to-immune-stimulants-and-nervous-necrosis-virus
#5
Thirunavukkarasu Periyasamy, Joan Tang Xiao Joe, Ming-Wei Lu
ADARs are RNA editing catalysts that bind double-stranded RNA and convert adenosine to inosine, a process that can lead to destabilization of dsRNA structures and suppression of mRNA translation. In mammals, ADAR1 genes are involved in various cellular pathways, including interferon (IFN)-mediated response. However, the function of fish ADAR1 remains unclear. We report here the cloning of ADAR1 in Malabar grouper (Epinephelus malabaricus) (MgADAR1) and its response to various immune stimulants. The MgADAR1 cDNA is 5371-bp long, consisting of an open reading frame encoding a putative protein of 1381 amino acids, a 235-nt 5'-terminal untranslated region (UTR), and a 990-nt 3'-UTR...
October 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29017567/impairment-of-igf2-gene-expression-in-prostate-cancer-is-triggered-by-epigenetic-dysregulation-of-igf2-dmr0-and-its-interaction-with-klf4
#6
Undraga Schagdarsurengin, Angela Lammert, Natalie Schunk, Diana Sheridan, Stefan Gattenloehner, Klaus Steger, Florian Wagenlehner, Temuujin Dansranjavin
BACKGROUND: Human cancer cells often exhibit impaired IGF2 expression and the underlying mechanisms are multifaceted and complex. Besides the well-known imprinting control region IGF2/H19-ICR, the involvement of a differentially methylated region in the promoter P0 of IGF2 gene (IGF2-DMR0) has been suggested. Here, we evaluate several mechanisms potentially leading to up- and/or down-regulation of IGF2 expression in prostate cancer and present a novel role of Kruppel-like factor 4 (KLF4) as a transcriptional regulator of IGF2 binding in IGF2-DMR0...
October 10, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28987236/associations-of-cord-blood-metabolites-with-perinatal-characteristics-newborn-anthropometry-and-cord-blood-hormones-in-project-viva
#7
Wei Perng, Sheryl L Rifas-Shiman, Scott McCulloch, Leda Chatzi, Christos Mantzoros, Marie-France Hivert, Emily Oken
CONTEXT: Metabolomics has emerged as a powerful tool to characterize biomarkers and elucidate physiological processes underlying adverse health outcomes. Little is known of these relationships during gestation and infancy, which are critical period for development of metabolic disease risk. OBJECTIVES: To identify cord blood metabolite patterns associated with birth size; and to investigate relations of the birth size-associated metabolite patterns, and a branched chain amino acid (BCAA) metabolite pattern with a range of newborn and perinatal characteristics...
November 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28986999/one-step-affinity-capture-and-precipitation-for-improved-purification-of-an-industrial-monoclonal-antibody-using-z-elp-functionalized-nanocages
#8
Andrew R Swartz, Xuankuo Xu, Steven J Traylor, Zheng J Li, Wilfred Chen
Protein A chromatography has been identified as a potential bottleneck in the monoclonal antibody production platform, leading to increased interest in non-chromatographic capture technologies. Affinity precipitation using environmentally responsive, Z-domain-elastin-like polypeptide (Z-ELP) fusion proteins has been shown to be a promising alternative. However, elevated temperature and salt concentrations necessary for precipitation resulted in decreased antibody monomer content and reduced purification capacity...
October 7, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28960389/the-other-face-of-an-editor-adar1-functions-in-editing-independent-ways
#9
REVIEW
Konstantin Licht, Michael F Jantsch
The RNA editing enzyme ADAR1 seemingly has more functions besides RNA editing. Mouse models lacking ADAR1 and sensors of foreign RNA show that RNA editing by ADAR1 plays a crucial role in the innate immune response. Still, RNA editing alone cannot explain all observed phenotypes. Thus, additional roles for ADAR1 must exist. Binding of ADAR1 to RNA is independent of its RNA editing function. Thus, ADAR1 may compete with other RNA-binding proteins. A very recent manuscript elaborates on this and reports competition of ADAR1 with STAUFEN1, thereby modulating RNA-degradation...
September 28, 2017: BioEssays: News and Reviews in Molecular, Cellular and Developmental Biology
https://www.readbyqxmd.com/read/28938067/a-single-chain-photoswitchable-crispr-cas9-architecture-for-light-inducible-gene-editing-and-transcription
#10
Xin X Zhou, Xinzhi Zou, Hokyung K Chung, Yuchen Gao, Yanxia Liu, Lei S Qi, Michael Z Lin
Optical control of CRISPR-Cas9-derived proteins would be useful for restricting gene editing or transcriptional regulation to desired times and places. Optical control of Cas9 functions has been achieved with photouncageable unnatural amino acids or by using light-induced protein interactions to reconstitute Cas9-mediated functions from two polypeptides. However, these methods have only been applied to one Cas9 species and have not been used for optical control of different perturbations at two genes. Here, we use photodissociable dimeric fluorescent protein domains to engineer single-chain photoswitchable Cas9 (ps-Cas9) proteins in which the DNA-binding cleft is occluded at baseline and opened upon illumination...
September 29, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28925810/ube3a-mediated-regulation-of-imprinted-genes-and-epigenome-wide-marks-in-human-neurons
#11
S Jesse Lopez, Keith Dunaway, M Saharul Islam, Charles Mordaunt, Annie Vogel Ciernia, Makiko Meguro-Horike, Shin-Ichi Horike, David J Segal, Janine LaSalle
The dysregulation of genes in neurodevelopmental disorders that lead to social and cognitive phenotypes is a complex, multilayered process involving both genetics and epigenetics. Parent-of-origin effects of deletion and duplication of the 15q11-q13 locus leading to Angelman, Prader-Willi, and Dup15q syndromes are due to imprinted genes, including UBE3A, which is maternally expressed exclusively in neurons. UBE3A encodes a ubiquitin E3 ligase protein with multiple downstream targets, including RING1B, which in turn monoubiquitinates histone variant H2A...
September 19, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28924040/a-b-z-junction-induced-by-an-a-a-mismatch-in-gac-repeats-in-the-gene-for-cartilage-oligomeric-matrix-protein-promotes-binding-with-the-hz%C3%AE-adar1-protein
#12
Narendar Kolimi, Yogeeshwar Ajjugal, Thenmalarchelvi Rathinavelan
GAC repeat expansion from five to seven in the exonic region of the gene for cartilage oligomeric matrix protein (COMP) leads to pseudoachondroplasia, a skeletal abnormality. However, the molecular mechanism by which GAC expansions in the COMP gene lead to skeletal dysplasias is poorly understood. Here, we used MD simulations which indicate that an A...A mismatch in a d(GAC)6.d(GAC)6 duplex induces negative supercoiling, leading to a local B-to-Z DNA transition. This transition facilitates the binding of d(GAC)7...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28867751/t-786c-variation-in-the-promoter-sequence-of-human-enos-gene-markedly-influences-its-expression-level
#13
Aliaa M Elakkad, Khaled Abou-Aisha, Sally I Hassanein, Mohamed Z Gad
This study investigated the role of the T-786C polymorphism (SNP) in the 5'-flanking sequence of the endothelial nitric oxide synthase gene (eNOS) on its expression level in vascular endothelium with the ultimate goal of shedding more light on the mechanisms by which genetic variations of eNOS might affect the vascular level of nitric oxide (NO). Sequences in the 5'-flanking region of eNOS gene were PCR-amplified using genomic DNA templates isolated from blood samples collected from cardiovascular disease (CVD) patients...
2017: Drug Discoveries & Therapeutics
https://www.readbyqxmd.com/read/28806396/inhibiting-myc-binding-to-the-e-box-dna-motif-by-me47-decreases-tumour-xenograft-growth
#14
L C Lustig, D Dingar, W B Tu, C Lourenco, M Kalkat, I Inamoto, R Ponzielli, W C W Chan, J A Shin, L Z Penn
Developing therapeutics to effectively inhibit the MYC oncoprotein would mark a key advance towards cancer patient care as MYC is deregulated in over 50% of human cancers. MYC deregulation is correlated with aggressive disease and poor patient outcome. Despite strong evidence in mouse models that inhibiting MYC would significantly impact tumour cell growth and patient survival, traditional approaches have not yet yielded the urgently needed therapeutic agents that directly target MYC. MYC functions through its interaction with MAX to regulate gene transcription by binding to E-box DNA response elements of MYC target genes...
August 14, 2017: Oncogene
https://www.readbyqxmd.com/read/28783694/zbp1-dai-is-an-innate-sensor-of-influenza-virus-triggering-the-nlrp3-inflammasome-and-programmed-cell-death-pathways
#15
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 (IFN)-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 double-stranded DNA 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. We demonstrated ZBP1-mediated sensing of the influenza A virus (IAV) proteins NP and PB1, triggering cell death and inflammatory responses via the receptor-interacting protein kinase 1 (RIPK1)-RIPK3-caspase-8 axis...
August 12, 2016: Science Immunology
https://www.readbyqxmd.com/read/28746399/coordination-of-matrix-attachment-and-atp-dependent-chromatin-remodeling-regulate-auxin-biosynthesis-and-arabidopsis-hypocotyl-elongation
#16
Kyounghee Lee, Pil Joon Seo
Hypocotyl elongation is extensively controlled by hormone signaling networks. In particular, auxin metabolism and signaling play key roles in light-dependent hypocotyl growth. The nuclear matrix facilitates organization of DNA within the nucleus, and dynamic interactions between nuclear matrix and DNA are related to gene regulation. Conserved scaffold/matrix attachment regions (S/MARs) are anchored to the nuclear matrix by the AT-HOOK MOTIF CONTAINING NUCLEAR LOCALIZED (AHL) proteins in Arabidopsis. Here, we found that ESCAROLA (ESC)/AHL27 and SUPPRESSOR OF PHYTOCHROME B-4 #3 (SOB3)/AHL29 redundantly regulate auxin biosynthesis in the control of hypocotyl elongation...
2017: PloS One
https://www.readbyqxmd.com/read/28716805/sensing-of-viral-and-endogenous-rna-by-zbp1-dai-induces-necroptosis
#17
Jonathan Maelfait, Layal Liverpool, Anne Bridgeman, Katherine B Ragan, Jason W Upton, Jan Rehwinkel
Nucleic acids are potent triggers for innate immunity. Double-stranded DNA and RNA adopt different helical conformations, including the unusual Z-conformation. Z-DNA/RNA is recognised by Z-binding domains (ZBDs), which are present in proteins implicated in antiviral immunity. These include ZBP1 (also known as DAI or DLM-1), which induces necroptosis, an inflammatory form of cell death. Using reconstitution and knock-in models, we report that mutation of key amino acids involved in Z-DNA/RNA binding in ZBP1's ZBDs prevented necroptosis upon infection with mouse cytomegalovirus...
September 1, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28714949/aspartate-%C3%AE-hydroxylase-disrupts-mitochondrial-dna-stability-and-function-in-hepatocellular-carcinoma
#18
C Tang, Y Hou, H Wang, K Wang, H Xiang, X Wan, Y Xia, J Li, W Wei, S Xu, Z Lei, T M Pawlik, H Wang, M Wu, F Shen
The mechanism of aberrant mitochondrial genome and function in hepatocellular carcinoma (HCC) remains largely unknown. Our previous study demonstrated an increased expression of aspartate β-hydroxylase (ASPH) in HCC tissues, which was associated with tumor invasiveness and a worse prognosis. Currently, we unexpectedly observed the presence of ASPH in purified mitochondrial protein fraction. In addition, immunostaining of both exogenously and endogenously expressed ASPH showed a colocalization with mitochondrial biomarkers...
July 17, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28707750/arterial-immune-protein-expression-demonstrates-the-complexity-of-immune-responses-in-kawasaki-disease-arteritis
#19
S A Cameron, S M White, D Arrollo, S T Shulman, A H Rowley
A more complete understanding of immune-mediated damage to the coronary arteries in children with Kawasaki disease (KD) is required for improvements in patient treatment and outcomes. We recently reported the transcriptional profile of KD coronary arteritis, and in this study sought to determine protein expression of transcriptionally up-regulated immune genes in KD coronary arteries from the first 2 months after disease onset. We examined the coronary arteries of 12 fatal KD cases and 13 childhood controls for expression of a set of proteins whose genes were highly up-regulated in the KD coronary artery transcriptome: allograft inflammatory factor 1 (AIF1), interleukin 18 (IL-18), CD74, CD1c, CD20 (MS4A1), Toll-like receptor 7 (TLR-7) and Z-DNA binding protein 1 (ZBP1)...
November 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28692032/epigenetic-silencing-of-microrna-137-enhances-asct2-expression-and-tumor-glutamine-metabolism
#20
J Dong, D Xiao, Z Zhao, P Ren, C Li, Y Hu, J Shi, H Su, L Wang, H Liu, B Li, P Gao, G Qing
Tumor cells must activate specific transporters to meet their increased glutamine metabolic demands. Relative to other glutamine transporters, the ASC family transporter 2 (ASCT2, also called SLC1A5) is profoundly elevated in a wide spectrum of human cancers to coordinate metabolic reprogramming and malignant transformation. Understanding the molecular mechanisms whereby tumor cells frequently upregulate this transporter is therefore vital to develop potential strategies for transporter-targeted therapies. Combining in-silico algorithms with systemic experimental screening, we herein identify the tumor suppressor microRNA, miR-137, as an essential regulator that targets ASCT2 and cancer cell glutamine metabolism...
July 10, 2017: Oncogenesis
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