当前位置： SCI文献检索 > NUCLEIC ACIDS RESEARCH期刊下所有文献 > Designer epigenome modifiers enable robust and sustained gene silencing in clinically relevant human cells.

Designer epigenome modifiers enable robust and sustained gene silencing in clinically relevant human cells.

Abstract：

:Targeted modulation of gene expression represents a valuable approach to understand the mechanisms governing gene regulation. In a therapeutic context, it can be exploited to selectively modify the aberrant expression of a disease-causing gene or to provide the target cells with a new function. Here, we have established a novel platform for achieving precision epigenome editing using designer epigenome modifiers (DEMs). DEMs combine in a single molecule a DNA binding domain based on highly specific transcription activator-like effectors (TALEs) and several effector domains capable of inducing DNA methylation and locally altering the chromatin structure to silence target gene expression. We designed DEMs to target two human genes, CCR5 and CXCR4, with the aim of epigenetically silencing their expression in primary human T lymphocytes. We observed robust and sustained target gene silencing associated with reduced chromatin accessibility, increased promoter methylation at the target sites and undetectable changes in global gene expression. Our results demonstrate that DEMs can be successfully used to silence target gene expression in primary human cells with remarkably high specificity, paving the way for the establishment of a potential new class of therapeutics.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Mlambo T,Nitsch S,Hildenbeutel M,Romito M,Müller M,Bossen C,Diederichs S,Cornu TI,Cathomen T,Mussolino C

doi

10.1093/nar/gky171

subject

Has Abstract

pub_date

2018-05-18 00:00:00

pages

4456-4468

issue

9

eissn

0305-1048

issn

1362-4962

pii

4925758

journal_volume

46

pub_type

杂志文章

相关文献

NUCLEIC ACIDS RESEARCH文献大全
  • The MIGenAS integrated bioinformatics toolkit for web-based sequence analysis.

    abstract：:We describe a versatile and extensible integrated bioinformatics toolkit for the analysis of biological sequences over the Internet. The web portal offers convenient interactive access to a growing pool of chainable bioinformatics software tools and databases that are centrally installed and maintained by the RZG. Cur...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkl254

    authors： Rampp M,Soddemann T,Lederer H

    更新日期：2006-07-01 00:00:00

  • TFIIH is an elongation factor of RNA polymerase I.

    abstract：:TFIIH is a multisubunit factor essential for transcription initiation and promoter escape of RNA polymerase II and for the opening of damaged DNA double strands in nucleotide excision repair (NER). In this study, we have analyzed at which step of the transcription cycle TFIIH is essential for transcription by RNA poly...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkr746

    authors： Assfalg R,Lebedev A,Gonzalez OG,Schelling A,Koch S,Iben S

    更新日期：2012-01-01 00:00:00

  • Evidence for three distinct D proteins, which react differentially with anti-Sm autoantibodies, in the cores of the major snRNPs U1, U2, U4/U6 and U5.

    abstract：:Electrophoresis of the mixture of proteins from purified snRNPs U1, U2, U4/U6 and U5 on SDS-polyacrylamide gels that had been allowed to polymerise in the presence of high TEMED concentrations have revealed the presence of proteins in the snRNPs that previously had eluded detection. The most striking case is that of p...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/18.22.6475

    authors： Lehmeier T,Foulaki K,Lührmann R

    更新日期：1990-11-25 00:00:00

  • The bacterial and mitochondrial ribosomal A-site molecular switches possess different conformational substates.

    abstract：:The A site of the small ribosomal subunit participates in the fidelity of decoding by switching between two states, a resting 'off' state and an active decoding 'on' state. Eight crystal structures of RNA duplexes containing two minimal decoding A sites of the Homo sapiens mitochondrial wild-type, the A1555G mutant or...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkn112

    authors： Kondo J,Westhof E

    更新日期：2008-05-01 00:00:00

  • Base specificity in the interaction of ethidium with synthetic polyribonucleotides.

    abstract：:Base specificity in the interaction of ethidium with double stranded synthetic RNA homopolymers has been studied by means of spectroscopic (UV-visible absorption and fluorescence), microcalorimetric and dilatometric techniques. The results show a strong base specificity in this interaction, the association constant wi...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/15.14.5803

    authors： Babayan Y,Manzini G,Xodo LE,Quadrifoglio F

    更新日期：1987-07-24 00:00:00

  • Fluoride-cleavable biotinylation phosphoramidite for 5'-end-labeling and affinity purification of synthetic oligonucleotides.

    abstract：:A fluoride-cleavable phosphoramidite for biotinylation was designed, synthesized and coupled efficiently to the 5'-end of DNA on an automatic synthesizer. The diisopropylsilyl acetal functionality was used to link the biotin moiety through a tertiary hydroxide group to the 5'-end of DNA. This linkage proved to be comp...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkg130

    authors： Fang S,Bergstrom DE

    更新日期：2003-01-15 00:00:00

  • Recognition of prokaryotic promoters based on a novel variable-window Z-curve method.

    abstract：:Transcription is the first step in gene expression, and it is the step at which most of the regulation of expression occurs. Although sequenced prokaryotic genomes provide a wealth of information, transcriptional regulatory networks are still poorly understood using the available genomic information, largely because a...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkr795

    authors： Song K

    更新日期：2012-02-01 00:00:00

  • Differentially regulated malate synthase genes participate in carbon and nitrogen metabolism of S. cerevisiae.

    abstract：:We have isolated a second gene (MLS1), which in addition to DAL7, encodes malate synthase from S. cerevisiae. Expression of the two genes is specific for their physiological roles in carbon and nitrogen metabolism. Expression of MLS1, which participates in the utilization of non-fermentable carbon sources, is sensitiv...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/20.21.5677

    authors： Hartig A,Simon MM,Schuster T,Daugherty JR,Yoo HS,Cooper TG

    更新日期：1992-11-11 00:00:00

  • The integrase family of tyrosine recombinases: evolution of a conserved active site domain.

    abstract：:The integrases are a diverse family of tyrosine recombinases which rearrange DNA duplexes by means of conservative site-specific recombination reactions. Members of this family, of which the well-studied lambda Int protein is the prototype, were previously found to share four strongly conserved residues, including an ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/25.18.3605

    authors： Esposito D,Scocca JJ

    更新日期：1997-09-15 00:00:00

  • IL-3A virus infection of a Chlorella-like green alga induces a DNA restriction endonuclease with novel sequence specificity.

    abstract：:A type II restriction endonuclease, named CviJI, was isolated from a eukaryotic Chlorella-like green alga infected with the dsDNA containing virus IL-3A. CviJI is the first restriction endonuclease to recognize the sequence PuGCPy; CviJI cleaves DNA between the G and C. Methylation of the cytosine in PuGCPy sequences ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/15.15.6075

    authors： Xia YN,Burbank DE,Uher L,Rabussay D,Van Etten JL

    更新日期：1987-08-11 00:00:00

  • Transcriptional activation by mitochondrial transcription factor A involves preferential distortion of promoter DNA.

    abstract：:Mitochondrial transcription factor A (mtTFA/TFAM) is a nucleus-encoded, high-mobility-group-box (HMG-box) protein that regulates transcription of the mitochondrial genome by specifically recognizing light-strand and heavy-strand promoters (LSP, HSP1). TFAM also binds mitochondrial DNA in a non-sequence specific (NSS) ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkr787

    authors： Malarkey CS,Bestwick M,Kuhlwilm JE,Shadel GS,Churchill ME

    更新日期：2012-01-01 00:00:00

  • A novel E4BP4 element drives circadian expression of mPeriod2.

    abstract：:Period2 (Per2) is an essential component of the mammalian clock mechanism and robust circadian expression of Per2 is essential for the maintenance of circadian rhythms. Although recent studies have shown that the circadian E2 enhancer (a non-canonical E-box) accounts for most of the circadian transcriptional drive of ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkl868

    authors： Ohno T,Onishi Y,Ishida N

    更新日期：2007-01-01 00:00:00

  • RaftProt V2: understanding membrane microdomain function through lipid raft proteomes.

    abstract：:Cellular membranes feature dynamic submicrometer-scale lateral domains termed lipid rafts, membrane rafts or glycosphingolipid-enriched microdomains (GEM). Numerous proteomics studies have been conducted on the lipid raft proteome, however, interpretation of individual studies is limited by potential undefined contami...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gky948

    authors： Mohamed A,Shah AD,Chen D,Hill MM

    更新日期：2019-01-08 00:00:00

  • 2'-Alkynyl spin-labelling is a minimally perturbing tool for DNA structural analysis.

    abstract：:The determination of distances between specific points in nucleic acids is essential to understanding their behaviour at the molecular level. The ability to measure distances of 2-10 nm is particularly important: deformations arising from protein binding commonly fall within this range, but the reliable measurement of...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkaa086

    authors： Hardwick JS,Haugland MM,El-Sagheer AH,Ptchelkine D,Beierlein FR,Lane AN,Brown T,Lovett JE,Anderson EA

    更新日期：2020-04-06 00:00:00

  • The structural integrity exerted by N-terminal pyroglutamate is crucial for the cytotoxicity of frog ribonuclease from Rana pipiens.

    abstract：:Onconase, a cytotoxic ribonuclease from Rana pipiens, possesses pyroglutamate (Pyr) at the N-terminus and has a substrate preference for uridine-guanine (UG). To identify residues responsible for onconase's cytotoxicity, we cloned the rpr gene from genomic DNA and expressed it in Escherichia coli BL21(DE3). The recomb...

    journal_title：Nucleic acids research

    pub_type： 评论,杂志文章

    doi：10.1093/nar/gkg746

    authors： Liao YD,Wang SC,Leu YJ,Wang CF,Chang ST,Hong YT,Pan YR,Chen C

    更新日期：2003-09-15 00:00:00

  • alpha-DNA. I. Synthesis, characterization by high field 1H-NMR, and base-pairing properties of the unnatural hexadeoxyribonucleotide alpha-[d(CpCpTpTpCpC)] with its complement beta-[d(GpGpApApGpG)].

    abstract：:The novel deoxyribonucleotide alpha-[d(CpCpTpTpCpC)] and its complement beta-[d(GpGpApApGpG)] were synthesized by the phosphotriester method. 1H-NMR-NOE examination of the alpha-hexamer revealed that the cytosine and thymine bases appear to adopt anti conformations in this strand. In addition the deoxyribose of the th...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/14.12.5019

    authors： Morvan F,Rayner B,Imbach JL,Chang DK,Lown JW

    更新日期：1986-06-25 00:00:00

  • Effect of oxidative DNA damage in promoter elements on transcription factor binding.

    abstract：:Reactive oxygen species produced by endogenous metabolic activity and exposure to a multitude of exogenous agents impact cells in a variety of ways. The DNA base damage 8-oxodeoxyguanosine (8-oxodG) is a prominent indicator of oxidative stress and has been well-characterized as a premutagenic lesion in mammalian cells...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/27.15.3213

    authors： Ghosh R,Mitchell DL

    更新日期：1999-08-01 00:00:00

  • 2'-O-[2-[(N,N-dimethylamino)oxy]ethyl]-modified oligonucleotides inhibit expression of mRNA in vitro and in vivo.

    abstract：:Synthesis and antisense activity of oligonucleotides modified with 2'-O-[2-[(N,N-dimethylamino)oxy] ethyl] (2'-O-DMAOE) are described. The 2'-O-DMAOE-modified oligonucleotides showed superior metabolic stability in mice. The phosphorothioate oligonucleotide 'gapmers', with 2'-O-DMAOE- modified nucleoside residues at t...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkh220

    authors： Prakash TP,Johnston JF,Graham MJ,Condon TP,Manoharan M

    更新日期：2004-02-03 00:00:00

  • A thermostable endonuclease III homolog from the archaeon Pyrobaculum aerophilum.

    abstract：:Pyrimidine adducts in cellular DNA arise from modification of the pyrimidine 5,6-double bond by oxidation, reduction or hydration. The biological outcome includes increased mutation rate and potential lethality. A major DNA N:-glycosylase responsible for the excision of modified pyrimidine bases is the base excision r...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/29.3.604

    authors： Yang H,Phan IT,Fitz-Gibbon S,Shivji MK,Wood RD,Clendenin WM,Hyman EC,Miller JH

    更新日期：2001-02-01 00:00:00

  • Drosophila melanogaster Dis3 N-terminal domains are required for ribonuclease activities, nuclear localization and exosome interactions.

    abstract：:Eukaryotic cells use numerous pathways to regulate RNA production, localization and stability. Several of these pathways are controlled by ribonucleases. The essential ribonuclease, Dis3, plays important roles in distinct RNA metabolic pathways. Despite much progress in understanding general characteristics of the Dis...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkq295

    authors： Mamolen M,Smith A,Andrulis ED

    更新日期：2010-09-01 00:00:00

  • Isolation and characterization of the activated B-cell factor 1 homolog in Caenorhabditis elegans.

    abstract：:Members of the basic helix-loop-helix (bHLH) family of transcription factors regulate a wide array of developmental processes in many cell types, including cell fate specification, differentiation and morphogenesis. Our studies describe the cloning of a gene from the nematode Caenorhabditis elegans that is closely rel...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/29.21.4423

    authors： Nguyen L,Round J,O'Connell R,Geurts P,Funes-Duran M,Wong J,Jongeward G,Vierra CA

    更新日期：2001-11-01 00:00:00

  • Interaction between RECQL4 and OGG1 promotes repair of oxidative base lesion 8-oxoG and is regulated by SIRT1 deacetylase.

    abstract：:OGG1 initiated base excision repair (BER) is the major pathway for repair of oxidative DNA base damage 8-oxoguanine (8-oxoG). Here, we report that RECQL4 DNA helicase, deficient in the cancer-prone and premature aging Rothmund-Thomson syndrome, physically and functionally interacts with OGG1. RECQL4 promotes catalytic...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkaa392

    authors： Duan S,Han X,Akbari M,Croteau DL,Rasmussen LJ,Bohr VA

    更新日期：2020-07-09 00:00:00

  • Satellite DNA from Xenopus laevis: comparative analysis of 745 and 1037 base pair Hind III tandem repeats.

    abstract：:Highly repetitive Hind III restriction fragments of 0.72-0.76 KBP from total Xenopus laevis genomic DNA are organized in a tandem like arrangement. Cloning of these fragments in pBR 322 with subsequent restriction site mapping and nucleotide sequence analysis of some selected clones showed two different types of seque...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/11.20.6997

    authors： Meyerhof W,Tappeser B,Korge E,Knöchel W

    更新日期：1983-10-25 00:00:00

  • PCDDB: new developments at the Protein Circular Dichroism Data Bank.

    abstract：:The Protein Circular Dichroism Data Bank (PCDDB) has been in operation for more than 5 years as a public repository for archiving circular dichroism spectroscopic data and associated bioinformatics and experimental metadata. Since its inception, many improvements and new developments have been made in data display, se...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkw796

    authors： Whitmore L,Miles AJ,Mavridis L,Janes RW,Wallace BA

    更新日期：2017-01-04 00:00:00

  • Escherichia coli single-stranded DNA binding protein stimulates the DNA deoxyribophosphodiesterase activity of exonuclease I.

    abstract：:The E. coli single-stranded binding protein (SSB) has been demonstrated in vitro to be involved in a number of replicative, DNA renaturation, and protective functions. It was shown previously that SSB can interact with exonuclease I to stimulate the hydrolysis of single-stranded DNA. We demonstrate here that E. coli S...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/22.2.247

    authors： Sandigursky M,Franklin WA

    更新日期：1994-01-25 00:00:00

  • uORFdb--a comprehensive literature database on eukaryotic uORF biology.

    abstract：:Approximately half of all human transcripts contain at least one upstream translational initiation site that precedes the main coding sequence (CDS) and gives rise to an upstream open reading frame (uORF). We generated uORFdb, publicly available at http://cbdm.mdc-berlin.de/tools/uorfdb, to serve as a comprehensive li...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkt952

    authors： Wethmar K,Barbosa-Silva A,Andrade-Navarro MA,Leutz A

    更新日期：2014-01-01 00:00:00

  • The basidiomycete Lentinus edodes linear mitochondrial DNA plasmid contains a segment exhibiting a high autonomously replicating sequence activity in Saccharomyces cerevisiae.

    abstract：:A linear DNA plasmid, designated pLLE1, has been isolated from a mitochondrial fraction of a strain of Lentinus edodes. pLLE1(11.0 kbp) was sensitive to the 3'----5'-acting exonuclease III and resistant to the 5'----3'-acting lambda exonuclease. It showed no homology with mitochondrial and nuclear genomic DNAs of plas...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/18.6.1395

    authors： Katayose Y,Kajiwara S,Shishido K

    更新日期：1990-03-25 00:00:00

  • Conserved elements associated with ribosomal genes and their trans-splice acceptor sites in Caenorhabditis elegans.

    abstract：:The recent publication of the Caenorhabditis elegans cisRED database has provided an extensive catalog of upstream elements that are conserved between nematode genomes. We have performed a secondary analysis to determine which subsequences of the cisRED motifs are found in multiple locations throughout the C. elegans ...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/gkq003

    authors： Sleumer MC,Mah AK,Baillie DL,Jones SJ

    更新日期：2010-05-01 00:00:00

  • A new restriction endonuclease from Acetobacter pasteurianus.

    abstract：:A restriction endonuclease, ApaI, has been partially purified from Acetobacter pasteurianus. This enzyme cleaves bacteriophage lambda DNA and Simian virus 40 DNA at one site, adenovirus-2 DNA at more than nine sites, but it does not cleave phi X174 DNA nor plasmid pBR322 DNA. This enzyme recognizes the sequence (formu...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/11.13.4409

    authors： Seurinck J,Van de Voorde A,Van Montagu M

    更新日期：1983-07-11 00:00:00

  • Different dynamics in nuclear entry of subunits of the repair/transcription factor TFIIH.

    abstract：:We report here the different ways in which four subunits of the basal transcription/repair factor TFIIH (XPB, XPD, p62 and p44) and the damage recognition XPC repair protein can enter the nucleus. We examined their nuclear localization by transiently expressing the gene products tagged with the enhanced green fluoresc...

    journal_title：Nucleic acids research

    pub_type： 杂志文章

    doi：10.1093/nar/29.7.1574

    authors： Santagati F,Botta E,Stefanini M,Pedrini AM

    更新日期：2001-04-01 00:00:00