16,653 results match your criteria multiple dna-binding

Sequence-Specific Control of Mitochondrial Gene Transcription Using Programmable Synthetic Gene Switches Called MITO-PIPs.

Methods Mol Biol 2021 ;2275:217-225

Institute of Integrated Cell Material Sciences (WPI-iCeMS), Kyoto University Institute for Advanced Study, Kyoto, Japan.

Mitochondria possess multiple copies of mitochondrial DNA (mtDNA) that encode 37 genes and their transcription and replication get controlled by unique molecular codes different from that in the nuclear DNA. The mtDNA has been gaining increased attention as one of the critical therapeutic targets as mutations in them impair the function of mitochondria and cause mitochondrial diseases like MELAS. In this chapter, we describe artificial control of mitochondrial transcription based on mtDNA sequence information with a new type of compounds termed MITO-PIPs, which encompasses two domains: pyrrole-imidazole polyamide as DNA recognition domain and mitochondrial penetrating peptide as the mitochondria-targeting domain. Read More

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January 2021

Simple and versatile imaging of genomic loci in live mammalian cells and early pre-implantation embryos using CAS-LiveFISH.

Sci Rep 2021 Jun 9;11(1):12220. Epub 2021 Jun 9.

Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.

Visualizing the 4D genome in live cells is essential for understanding its regulation. Programmable DNA-binding probes, such as fluorescent clustered regularly interspaced short palindromic repeats (CRISPR) and transcription activator-like effector (TALE) proteins have recently emerged as powerful tools for imaging specific genomic loci in live cells. However, many such systems rely on genetically-encoded components, often requiring multiple constructs that each must be separately optimized, thus limiting their use. Read More

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Phosphorylation of Trans-active response DNA binding protein-of 43 kDa promotes its cytoplasmic aggregation and modulates its function in tau mRNA stability and exon 10 alternative splicing.

J Neurochem 2021 Jun 9. Epub 2021 Jun 9.

Key Laboratory of Neuroregeneration and Ministry of Education of Jiangsu, Co-innovation Center of Neuroregeneration, NMPA Key Laboratory for Research, Evaluation of Tissue Engineering Technology Products.

Trans-active response DNA-binding protein of 43 kDa (TDP-43) promotes tau mRNA instability and tau exon 10 inclusion. Aggregation of phosphorylated TDP-43 is associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). CK1ε phosphorylates TDP-43 at multiple sites, enhances its cytoplasmic aggregation and modu-lates its function in tau mRNA processing. Read More

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The Hox protein conundrum: The "specifics" of DNA binding for Hox proteins and their partners.

Dev Biol 2021 Jun 5. Epub 2021 Jun 5.

Department of Biology, The University of North Dakota, USA. Electronic address:

Homeotic genes (Hox genes) are homeodomain-transcription factors involved in conferring segmental identity along the anterior-posterior body axis. Molecular characterization of HOX protein function raises some interesting questions regarding the source of the binding specificity of the HOX proteins. How do HOX proteins regulate common and unique target specificity across space and time? This review attempts to summarize and interpret findings in this area, largely focused on results from in vitro and in vivo studies in Drosophila and mouse systems. Read More

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Pre-diagnostic DNA methylation patterns differ according to mammographic breast density amongst women who subsequently develop breast cancer: a case-only study in the EPIC-Florence cohort.

Breast Cancer Res Treat 2021 Jun 8. Epub 2021 Jun 8.

Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Via Cosimo il Vecchio 2, 50141, Florence, Italy.

Purpose: Mammographic breast density (MBD) is a marker of increased breast cancer (BC) risk, yet much remains to be clarified about the underlying mechanisms. We investigated whether DNA methylation patterns differ between high- vs. low-MBD women who developed BC during an 8. Read More

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Recognition of a tandem lesion by DNA bacterial formamidopyrimidine glycosylases explored combining molecular dynamics and machine learning.

Comput Struct Biotechnol J 2021 30;19:2861-2869. Epub 2021 Apr 30.

Univ. Lyon, ENS de Lyon, CNRS UMR 5182, Université Claude Bernard Lyon 1, Laboratoire de Chimie, F69342 Lyon, France.

The combination of several closely spaced DNA lesions, which can be induced by a single radical hit, constitutes a hallmark in the DNA damage landscape and radiation chemistry. The occurrence of such a tandem base lesion gives rise to a strong coupling with the double helix degrees of freedom and induces important structural deformations, in contrast to DNA strands containing a single oxidized nucleobase. Although such complex lesions are known to be refractory to repair by DNA glycosylases, there is still a lack of structural evidence to rationalize these phenomena. Read More

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The mechanism of action of the SSB interactome reveals it is the first OB-fold family of genome guardians in prokaryotes.

Piero R Bianco

Protein Sci 2021 Jun 5. Epub 2021 Jun 5.

Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, Nebraska, USA.

The single-stranded DNA binding protein (SSB) is essential to all aspects of DNA metabolism in bacteria. This protein performs two distinct, but closely intertwined and indispensable functions in the cell. SSB binds to single-stranded DNA (ssDNA) and at least 20 partner proteins resulting in their regulation. Read More

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Pleiotropic effects of ActVI-ORFA as an unusual regulatory factor identified in the biosynthetic pathway of actinorhodin in Streptomyces coelicolor.

Microbiol Res 2021 May 27;250:126792. Epub 2021 May 27.

Helmholtz International Lab for Anti-Infectives, Shandong University-Helmholtz Institute of Biotechnology, State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, PR China; The College of Life Sciences, Central China Normal University, Wuhan, 430079, PR China. Electronic address:

Regulatory networks play critical roles in controlling the the biosynthesis of natural products in Streptomyces. ActVI-ORFA, a regulatory factor encoded by the actinorhodin biosynthetic gene cluster (act cluster), positively controls the production of actinorhodin (ACT) in Streptomyces coelicolor, although its regulatory mechanism remains obscure. This study aimed to identify the regulatory targets of ActVI-ORFA. Read More

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Enhanced Accumulation of Cisplatin in Ovarian Cancer Cells from Combination with Wedelolactone and Resulting Inhibition of Multiple Epigenetic Drivers.

Drug Des Devel Ther 2021 25;15:2211-2227. Epub 2021 May 25.

Eman Research Journal, Eman Research, Sydney, NSW, Australia.

Purpose: Cisplatin resistance is a major concern in ovarian cancer treatment. The aim of this study was to investigate if wedelolactone could perform better in resistant ovarian cancer cells when used in combination with cisplatin.

Methods: Growth inhibitory potential of wedelolactone and cisplatin was investigated through MTT reduction assay in ovarian cancer cell lines including A2780 (sensitive), A2780 (cisplatin resistant) and A2780 Resistance factor (RF) of drugs was determined in these three cell lines. Read More

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[Transcription Factor MTF-1 Involved in the Cellular Response to Zinc].

Fuminori Otsuka

Yakugaku Zasshi 2021 ;141(6):857-867

Laboratory of Molecular Environmental Health, Faculty of Pharma-Sciences, Teikyo University.

Heavy metals, both toxic and essential, have long been an important research focus in life science. To investigate the intracellular actions of heavy metals at the molecular level, I have been exploring protein factors involved in induction of metallothionein (MT) genes by heavy metals that specifically bind to a metal responsive element (MRE) in the region upstream of the human MT-IIA gene. Purification of a zinc-dependent MRE-binding factor, and cloning of its cDNA identified a sequence identical to that of metal-responsive transcription factor-1 (MTF-1). Read More

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January 2021

The Role of AP-1 Transcription Factors in Plasma Cell Biology and Multiple Myeloma Pathophysiology.

Cancers (Basel) 2021 May 12;13(10). Epub 2021 May 12.

Department of Internal Medicine II, University Hospital Krems, Mitterweg 10, 3500 Krems an der Donau, Austria.

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by the clonal expansion of malignant plasma cells within the bone marrow. Activator Protein-1 (AP-1) transcription factors (TFs), comprised of the JUN, FOS, ATF and MAF multigene families, are implicated in a plethora of physiologic processes and tumorigenesis including plasma cell differentiation and MM pathogenesis. Depending on the genetic background, the tumor stage, and cues of the tumor microenvironment, specific dimeric AP-1 complexes are formed. Read More

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Ubiquitin-Mediated Control of ETS Transcription Factors: Roles in Cancer and Development.

Int J Mol Sci 2021 May 12;22(10). Epub 2021 May 12.

Queen's Medical Centre, School of Life Sciences, University of Nottingham, Nottingham NG7 2UH, UK.

Genome expansion, whole genome and gene duplication events during metazoan evolution produced an extensive family of genes whose members express transcription factors with a conserved winged helix-turn-helix DNA-binding domain. Unravelling their biological roles has proved challenging with functional redundancy manifest in overlapping expression patterns, a common consensus DNA-binding motif and responsiveness to mitogen-activated protein kinase signalling. Key determinants of the cellular repertoire of ETS proteins are their stability and turnover, controlled largely by the actions of selective E3 ubiquitin ligases and deubiquitinases. Read More

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A sequence-based multiple kernel model for identifying DNA-binding proteins.

BMC Bioinformatics 2021 May 31;22(Suppl 3):291. Epub 2021 May 31.

School of Computer Science and Engineering, Central South University, Changsha, People's Republic of China.

Background: DNA-Binding Proteins (DBP) plays a pivotal role in biological system. A mounting number of researchers are studying the mechanism and detection methods. To detect DBP, the tradition experimental method is time-consuming and resource-consuming. Read More

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Cooperative DNA looping by PRC2 complexes.

Nucleic Acids Res 2021 May 31. Epub 2021 May 31.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.

Polycomb repressive complex 2 (PRC2) is an essential protein complex that silences gene expression via post-translational modifications of chromatin. This paper combined homology modeling, atomistic and coarse-grained molecular dynamics simulations, and single-molecule force spectroscopy experiments to characterize both its full-length structure and PRC2-DNA interactions. Using free energy calculations with a newly parameterized protein-DNA force field, we studied a total of three potential PRC2 conformations and their impact on DNA binding and bending. Read More

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ChIP-seq Analysis of the Global Regulator Vfr Reveals Novel Insights Into the Biocontrol Agent FD6.

Front Microbiol 2021 14;12:667637. Epub 2021 May 14.

College of Horticulture and Plant Protection, Yangzhou University, Yangzhou, China.

Many strains produce the antibiotics pyoluteorin (PLT) and 2,4-diacetylphloroglucinol (2,4-DAPG), both of which have antimicrobial properties. The biosynthesis of these metabolites is typically controlled by multiple regulatory factors. Virulence factor regulator (Vfr) is a multifunctional DNA-binding regulator that modulates 2,4-DAPG biosynthesis in FD6. Read More

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The landscape of gene co-expression modules correlating with prognostic genetic abnormalities in AML.

J Transl Med 2021 May 29;19(1):228. Epub 2021 May 29.

Department of Hematology, China-Japan Friendship Hospital, Yinghua East Street, Beijing, China.

Background: The heterogenous cytogenetic and molecular variations were harbored by AML patients, some of which are related with AML pathogenesis and clinical outcomes. We aimed to uncover the intrinsic expression profiles correlating with prognostic genetic abnormalities by WGCNA.

Methods: We downloaded the clinical and expression dataset from BeatAML, TCGA and GEO database. Read More

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TbTRF suppresses the TERRA level and regulates the cell cycle-dependent TERRA foci number with a TERRA binding activity in its C-terminal Myb domain.

Nucleic Acids Res 2021 06;49(10):5637-5653

Center for Gene Regulation in Health and Disease, Department of Biological, Geological, and Environmental Sciences, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Avenue, Cleveland, OH 44115, USA.

Telomere repeat-containing RNA (TERRA) has been identified in multiple organisms including Trypanosoma brucei, a protozoan parasite that causes human African trypanosomiasis. T. brucei regularly switches its major surface antigen, VSG, to evade the host immune response. Read More

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DNA-Bound p53-DNA-Binding Domain Interconverts between Multiple Conformations: Implications for Partner Protein Recognition.

J Phys Chem B 2021 Jun 27;125(22):5832-5837. Epub 2021 May 27.

Department of Biophysics, Bose Institute, P1-12, C.I.T. Scheme VII M, Kolkata 700054, India.

Protein-protein interaction networks are critical components of cellular regulation. Hub proteins, defined by their ability to interact with numerous protein partners, are the pivots of these networks. A hypothesis that an ensemble of rapidly interconverting conformational states contributes significantly to the ability of hub proteins to interact with diverse partners has been proposed. Read More

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Genome-wide comparative analyses of GATA transcription factors among 19 Arabidopsis ecotype genomes: Intraspecific characteristics of GATA transcription factors.

PLoS One 2021 26;16(5):e0252181. Epub 2021 May 26.

InfoBoss Inc., Gangnam-gu, Seoul, Republic of Korea.

GATA transcription factors (TFs) are widespread eukaryotic regulators whose DNA-binding domain is a class IV zinc finger motif (CX2CX17-20CX2C) followed by a basic region. Due to the low cost of genome sequencing, multiple strains of specific species have been sequenced: e.g. Read More

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Plastid Gene Transcription: An Update on Promoters and RNA Polymerases.

Methods Mol Biol 2021 ;2317:49-76

Department of Biology and Biotechnology, University of Bochum, Bochum, Germany.

Chloroplasts, the sites of photosynthesis and sources of reducing power, are at the core of the success story that sets apart autotrophic plants from most other living organisms. Along with their fellow organelles (e.g. Read More

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January 2021

The physiological role of estrogen receptor functional domains.

Essays Biochem 2021 May 24. Epub 2021 May 24.

Receptor Biology Section, Reproductive and Developmental Biology Laboratory, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, United States.

Estrogen receptor (ER) is a member of the nuclear receptor superfamily whose members share conserved domain structures, including a DNA-binding domain (DBD) and ligand-binding domain (LBD). Estrogenic chemicals work as ligands for activation or repression of ER-mediated transcriptional activity derived from two transactivation domains: AF-1 and AF-2. AF-2 is localized in the LBD, and helix 12 of the LBD is essential for controlling AF-2 functionality. Read More

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PredictProtein - Predicting Protein Structure and Function for 29 Years.

Nucleic Acids Res 2021 May 17. Epub 2021 May 17.

TUM (Technical University of Munich) Department of Informatics, Bioinformatics & Computational Biology - i12, Boltzmannstr 3, 85748 Garching/Munich, Germany.

Since 1992 PredictProtein (https://predictprotein.org) is a one-stop online resource for protein sequence analysis with its main site hosted at the Luxembourg Centre for Systems Biomedicine (LCSB) and queried monthly by over 3,000 users in 2020. PredictProtein was the first Internet server for protein predictions. Read More

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Cell-Based Delivery Approaches for DNA-Binding Domains into the Central Nervous System.

Curr Neuropharmacol 2021 May 17. Epub 2021 May 17.

UC Davis Medical Center, Department of Neurology. United States.

Advancements in programmable DNA-binding proteins (DBDs) that target the genome, such as zinc fingers, transcription activator-like effectors, and Cas9, have broadened drug target design beyond traditional protein substrates. Effective delivery methodologies remain a major barrier in targeting the central nervous system. Currently, adeno-associated virus is the most well-validated delivery system for the delivery of DBDs towards the central nervous with multiple, on-going clinical trials. Read More

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A Pathogenic Missense Variant in Causes Common Variable Immunodeficiency Due to Detrimental Protein Damage.

Front Immunol 2021 27;12:621503. Epub 2021 Apr 27.

Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

In common variable immunodeficiency (CVID), heterozygous damaging variants represent the most frequent monogenic cause. encodes the precursor p105, which undergoes proteasomal processing to generate the mature NF-κB transcription factor subunit p50. The majority of sequence changes comprises missense variants of uncertain significance (VUS), each requiring functional evaluation to assess causality, particularly in families with multiple affected members presenting with different phenotypes. Read More

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CHD4 as an important mediator in regulating the malignant behaviors of colorectal cancer.

Int J Biol Sci 2021 12;17(7):1660-1670. Epub 2021 Apr 12.

Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

Colorectal cancer (CRC) has ranked first in terms of incidence in Taiwan. Surgical resection combined with chemo-, radio-, or targeted-therapies are the main treatments for CRC patients in current clinical practice. However, many CRC patients still respond poorly to these treatments, leading to tumor recurrence and an unacceptably high incidence of metastasis and death. Read More

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Transcriptional reprogramming by oxidative stress occurs within a predefined chromatin accessibility landscape.

Free Radic Biol Med 2021 May 13;171:319-331. Epub 2021 May 13.

Department of Biomedical Sciences, University of Minnesota Medical School, Duluth, MN, 55812, USA. Electronic address:

Reactive oxygen species (ROS) are important signaling molecules in many physiological processes, yet excess ROS leads to cell damage and can lead to pathology. Accordingly, cells need to maintain tight regulation of ROS levels, and ROS-responsive transcriptional reprogramming is central to this process. Although it has long been recognized that oxidative stress leads to rapid, significant changes in gene expression, the impact of oxidative stress on the underlying chromatin accessibility landscape remained unclear. Read More

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Selective Nonmethylated CpG DNA Recognition Mechanism of Cysteine Clamp Domains.

J Am Chem Soc 2021 May 13;143(20):7688-7697. Epub 2021 May 13.

Beijing Nuclear Magnetic Resonance Center, College of Chemistry and Molecular Engineering, and School of Life Sciences, Peking University, Beijing 100871, China.

Methylation of DNA at CpG sites is a major mark for epigenetic regulation, but how transcription factors are influenced by CpG methylation is not well understood. Here, we report the molecular mechanisms of how the TCF (T-cell factor) and GEF (glucose transporter 4 enhancer factor) families of proteins selectively target unmethylated DNA sequences with a C-clamp type zinc finger domain. The structure of the C-clamp domain from human GEF family protein HDBP1 (C-clamp) in complex with DNA was determined using NMR spectroscopy, which adopts a unique zinc finger fold and selectively binds RCCGG (R = A/G) DNA sequences with an "Arg···Trp-Lys-Lys" DNA recognition motif inserted in the major groove. Read More

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In-silico prediction of in-vitro protein liquid-liquid phase separation experiments outcomes with multi-head neural attention.

Bioinformatics 2021 May 13. Epub 2021 May 13.

SWITCH Lab, Leuven, KU, Belgium.

Motivation: Proteins able to undergo Liquid-Liquid Phase Separation (LLPS) in-vivo and in-vitro are drawing a lot of interest, due to their functional relevance for cell life. Nevertheless, the proteome-scale experimental screening of these proteins seems unfeasible, because besides being expensive and time consuming, LLPS is heavily influenced by multiple environmental conditions such as concentration, pH and temperature, thus requiring a combinatorial number of experiments for each protein.

Results: To overcome this problem, we propose an Neural Network model able to predict the LLPS behavior of proteins given specified experimental conditions, effectively predicting the outcome of in-vitro experiments. Read More

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Characterization of a novel type III CRISPR-Cas effector provides new insights into the allosteric activation and suppression of the Cas10 DNase.

Cell Discov 2020 May 12;6(1):29. Epub 2020 May 12.

Microbial Technology Institute and State Key Laboratory of Microbial Technology, Shandong University, 72 Binhai Road, Jimo, 266237, Qingdao, Shandong, China.

Antiviral defense by type III CRISPR-Cas systems relies on two distinct activities of their effectors: the RNA-activated DNA cleavage and synthesis of cyclic oligoadenylate. Both activities are featured as indiscriminate nucleic acid cleavage and subjected to the spatiotemporal regulation. To yield further insights into the involved mechanisms, we reconstituted LdCsm, a lactobacilli III-A system in Escherichia coli. Read More

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The Cryo-EM Effect: Structural Biology of Neurodegenerative Disease Aggregates.

J Neuropathol Exp Neurol 2021 Jun;80(6):514-529

From the Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Neurogenerative diseases are characterized by diverse protein aggregates with a variety of microscopic morphologic features. Although ultrastructural studies of human neurodegenerative disease tissues have been conducted since the 1960s, only recently have near-atomic resolution structures of neurodegenerative disease aggregates been described. Solid-state nuclear magnetic resonance spectroscopy and X-ray crystallography have provided near-atomic resolution information about in vitro aggregates but pose logistical challenges to resolving the structure of aggregates derived from human tissues. Read More

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