MutSβ and histone deacetylase complexes promote expansions of trinucleotide repeats in human cells.

Abstract:

:Trinucleotide repeat (TNR) expansions cause at least 17 heritable neurological diseases, including Huntington's disease. Expansions are thought to arise from abnormal processing of TNR DNA by specific trans-acting proteins. For example, the DNA repair complex MutSβ (MSH2-MSH3 heterodimer) is required in mice for on-going expansions of long, disease-causing alleles. A distinctive feature of TNR expansions is a threshold effect, a narrow range of repeat units (∼30-40 in humans) at which mutation frequency rises dramatically and disease can initiate. The goal of this study was to identify factors that promote expansion of threshold-length CTG•CAG repeats in a human astrocytic cell line. siRNA knockdown of the MutSβ subunits MSH2 or MSH3 impeded expansions of threshold-length repeats, while knockdown of the MutSα subunit MSH6 had no effect. Chromatin immunoprecipitation experiments indicated that MutSβ, but not MutSα, was enriched at the TNR. These findings imply a direct role for MutSβ in promoting expansion of threshold-length CTG•CAG tracts. We identified the class II deacetylase HDAC5 as a novel promoting factor for expansions, joining the class I deacetylase HDAC3 that was previously identified. Double knockdowns were consistent with the possibility that MutSβ, HDAC3 and HDAC5 act through a common pathway to promote expansions of threshold-length TNRs.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Gannon AM,Frizzell A,Healy E,Lahue RS

doi

10.1093/nar/gks810

subject

Has Abstract

pub_date

2012-11-01 00:00:00

pages

10324-33

issue

20

eissn

0305-1048

issn

1362-4962

pii

gks810

journal_volume

40

pub_type

杂志文章
  • Blotting of RNA onto ion exchange paper allowing subsequent characterization by in situ translation in addition to blot hybridization.

    abstract::We present the preparation of an ion exchange paper which can be used as a solid carrier in the transfer of RNA from gels. In addition to detection by blot hybridization to specific probes, transferred RNA can be characterized by cell-free translation in situ. Preparation of the paper is simple, inexpensive and reprod...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/10.16.4831

    authors: Saris CJ,Franssen HJ,Heuyerjans JH,van Eenbergen J,Bloemers HP

    更新日期:1982-08-25 00:00:00

  • MAGIA²: from miRNA and genes expression data integrative analysis to microRNA-transcription factor mixed regulatory circuits (2012 update).

    abstract::MAGIA(2) (http://gencomp.bio.unipd.it/magia2) is an update, extension and evolution of the MAGIA web tool. It is dedicated to the integrated analysis of in silico target prediction, microRNA (miRNA) and gene expression data for the reconstruction of post-transcriptional regulatory networks. miRNAs are fundamental post...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks460

    authors: Bisognin A,Sales G,Coppe A,Bortoluzzi S,Romualdi C

    更新日期:2012-07-01 00:00:00

  • ARTS: a web-based tool for the set-up of high-throughput genome-wide mapping panels for the SNP genotyping of mouse mutants.

    abstract::Genome-wide mapping in the identification of novel candidate genes has always been the standard method in genetics and genomics to correlate a clinically interesting phenotypic trait with a genotype. However, the performance of a mapping experiment using classical microsatellite approaches can be very time consuming. ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gki430

    authors: Klaften M,Hrabé de Angelis M

    更新日期:2005-07-01 00:00:00

  • Recent amplification of an alpha satellite DNA in humans.

    abstract::A repeat sequence 682 base pairs (bp) long produced by cleavage of human DNA with Xba I restriction enzyme is composed of four tandemly arranged subunits with lengths of 171, 170, 171, and 170 bp each. The sequence organization of the 682 bp Xba I repeat bears a striking resemblance to other complex satellite DNAs of ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/13.2.521

    authors: Gray KM,White JW,Costanzi C,Gillespie D,Schroeder WT,Calabretta B,Saunders GF

    更新日期:1985-01-25 00:00:00

  • Deep sequencing of small RNAs identifies canonical and non-canonical miRNA and endogenous siRNAs in mammalian somatic tissues.

    abstract::MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression. They are characterized by specific maturation processes defined by canonical and non-canonical biogenic pathways. Analysis of ∼0.5 billion sequences from mouse data sets derived from different tissues, developmental stages and cell types, partly...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks1474

    authors: Castellano L,Stebbing J

    更新日期:2013-03-01 00:00:00

  • Molecular modelling of the 3-D structure of RNA tetraloops with different nucleotide sequences.

    abstract::One surprisingly common element of RNA secondary structure consists of a hairpin capped by a four-base loop (or the tetraloop). Recently the 3-D structures of two RNA-tetraloops have been determined by NMR-studies. Both structures have a similar architecture: the first and the last bases of the loop form a hydrogen bo...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/21.19.4556

    authors: Kajava A,Rüterjans H

    更新日期:1993-09-25 00:00:00

  • Cold-sensitive mutants of Taq DNA polymerase provide a hot start for PCR.

    abstract::Although the thermophilic bacterium Thermus aquaticus grows optimally at 70 degrees C and cannot grow at moderate temperatures, its DNA polymerase I has significant activity at 20-37 degrees C. This activity is a bane to some PCRs, since it catalyzes non-specific priming. We report mutations of Klentaq (an N-terminal ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkg813

    authors: Kermekchiev MB,Tzekov A,Barnes WM

    更新日期:2003-11-01 00:00:00

  • Single-cell transcriptome analysis of Physcomitrella leaf cells during reprogramming using microcapillary manipulation.

    abstract::Next-generation sequencing technologies have made it possible to carry out transcriptome analysis at the single-cell level. Single-cell RNA-sequencing (scRNA-seq) data provide insights into cellular dynamics, including intercellular heterogeneity as well as inter- and intra-cellular fluctuations in gene expression tha...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkz181

    authors: Kubo M,Nishiyama T,Tamada Y,Sano R,Ishikawa M,Murata T,Imai A,Lang D,Demura T,Reski R,Hasebe M

    更新日期:2019-05-21 00:00:00

  • Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development.

    abstract::Co-option of cis-regulatory modules has been suggested as a mechanism for the evolution of expression sites during development. However, the extent and mechanisms involved in mobilization of cis-regulatory modules remains elusive. To trace the history of non-coding elements, which may represent candidate ancestral cis...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt030

    authors: Sanges R,Hadzhiev Y,Gueroult-Bellone M,Roure A,Ferg M,Meola N,Amore G,Basu S,Brown ER,De Simone M,Petrera F,Licastro D,Strähle U,Banfi S,Lemaire P,Birney E,Müller F,Stupka E

    更新日期:2013-04-01 00:00:00

  • Cleavage of the sarcin-ricin loop of 23S rRNA differentially affects EF-G and EF-Tu binding.

    abstract::Ribotoxins are potent inhibitors of protein biosynthesis and inactivate ribosomes from a variety of organisms. The ribotoxin alpha-sarcin cleaves the large 23S ribosomal RNA (rRNA) at the universally conserved sarcin-ricin loop (SRL) leading to complete inactivation of the ribosome and cellular death. The SRL interact...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkq151

    authors: García-Ortega L,Alvarez-García E,Gavilanes JG,Martínez-del-Pozo A,Joseph S

    更新日期:2010-07-01 00:00:00

  • Expression of the human cystic fibrosis transmembrane conductance regulator gene in the mouse lung after in vivo intratracheal plasmid-mediated gene transfer.

    abstract::As an approach to gene therapy for the respiratory manifestations of cystic fibrosis (CF), in vivo plasmid-mediated direct transfer of the normal CF transmembrane conductance regulator (CFTR) gene to the airway epithelium was investigated in mice. To evaluate the feasibility of this strategy, pRSVL, a plasmid composed...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/20.12.3233

    authors: Yoshimura K,Rosenfeld MA,Nakamura H,Scherer EM,Pavirani A,Lecocq JP,Crystal RG

    更新日期:1992-06-25 00:00:00

  • MolliGen, a database dedicated to the comparative genomics of Mollicutes.

    abstract::Bacteria belonging to the class Mollicutes were among the first ones to be selected for complete genome sequencing because of the minimal size of their genomes and their pathogenicity for humans and a broad range of animals and plants. At this time six genome sequences have been publicly released (Mycoplasma genitaliu...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkh114

    authors: Barré A,de Daruvar A,Blanchard A

    更新日期:2004-01-01 00:00:00

  • Autoregulation of MBNL1 function by exon 1 exclusion from MBNL1 transcript.

    abstract::Muscleblind-like proteins (MBNLs) are regulators of RNA metabolism. During tissue differentiation the level of MBNLs increases, while their functional insufficiency plays a crucial role in myotonic dystrophy (DM). Deep sequencing of RNA molecules cross-linked to immunoprecipitated protein particles (CLIP-seq) revealed...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkw1158

    authors: Konieczny P,Stepniak-Konieczna E,Taylor K,Sznajder LJ,Sobczak K

    更新日期:2017-02-28 00:00:00

  • The malaria parasite Plasmodium falciparum encodes members of the Puf RNA-binding protein family with conserved RNA binding activity.

    abstract::A novel class of RNA-binding proteins, Puf, regulates translation and RNA stability by binding to specific sequences in the 3'-untranslated region of target mRNAs. Members of this protein family share a conserved Puf domain consisting of eight 36 amino acid imperfect repeats. Here we report two Puf family member genes...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkf600

    authors: Cui L,Fan Q,Li J

    更新日期:2002-11-01 00:00:00

  • The MRE11-NBS1-RAD50 pathway is perturbed in SV40 large T antigen-immortalized AT-1, AT-2 and HL-1 cardiomyocytes.

    abstract::To investigate molecular controls of cardiomyocyte proliferation, we utilized cardiomyocytes induced to proliferate indefinitely by SV40 large T antigen (T-ag). In the T-ag-immortalized AT-1, AT-2 and HL-1 cardiomyocytes, normal cellular proteins associating with T-ag and p53 were identified, isolated and micro-sequen...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/28.15.2882

    authors: Lanson NA Jr,Egeland DB,Royals BA,Claycomb WC

    更新日期:2000-08-01 00:00:00

  • Identification of residues required for stalled-ribosome rescue in the codon-independent release factor YaeJ.

    abstract::The YaeJ protein is a codon-independent release factor with peptidyl-tRNA hydrolysis (PTH) activity, and functions as a stalled-ribosome rescue factor in Escherichia coli. To identify residues required for YaeJ function, we performed mutational analysis for in vitro PTH activity towards rescue of ribosomes stalled on ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt1280

    authors: Kogure H,Handa Y,Nagata M,Kanai N,Güntert P,Kubota K,Nameki N

    更新日期:2014-03-01 00:00:00

  • Efficient and seamless DNA recombineering using a thymidylate synthase A selection system in Escherichia coli.

    abstract::Lambda-red system-based recombinogenic engineering is a powerful new method to engineer DNA without the need for restriction enzymes or ligases. Here, we report the use of a single selectable marker to enhance the usefulness of this approach. The strategy is to utilize the thymidylate synthase A (thyA) gene, which enc...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gni059

    authors: Wong QN,Ng VC,Lin MC,Kung HF,Chan D,Huang JD

    更新日期:2005-03-30 00:00:00

  • The Mouse Genome Database genotypes::phenotypes.

    abstract::The Mouse Genome Database (MGD, http://www.informatics.jax.org/), integrates genetic, genomic and phenotypic information about the laboratory mouse, a primary animal model for studying human biology and disease. Information in MGD is obtained from diverse sources, including the scientific literature and external datab...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn886

    authors: Blake JA,Bult CJ,Eppig JT,Kadin JA,Richardson JE,Mouse Genome Database Group.

    更新日期:2009-01-01 00:00:00

  • Structural organization of mRNA complexes with major core mRNP protein YB-1.

    abstract::YB-1 is a universal major protein of cytoplasmic mRNPs, a member of the family of multifunctional cold shock domain proteins (CSD proteins). Depending on its amount on mRNA, YB-1 stimulates or inhibits mRNA translation. In this study, we have analyzed complexes formed in vitro at various YB-1 to mRNA ratios, including...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkh889

    authors: Skabkin MA,Kiselyova OI,Chernov KG,Sorokin AV,Dubrovin EV,Yaminsky IV,Vasiliev VD,Ovchinnikov LP

    更新日期:2004-10-19 00:00:00

  • Unrecognized sequence homologies may confound genome-wide association studies.

    abstract::Genome-wide association studies (GWAS) have become a preferred method to identify new genetic susceptibility loci. This technique aims to understanding the molecular etiology of common diseases, but in many cases, it has led to the identification of loci with no obvious biological relevance. Herein, we show that previ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks169

    authors: Galichon P,Mesnard L,Hertig A,Stengel B,Rondeau E

    更新日期:2012-06-01 00:00:00

  • Automated design of hammerhead ribozymes and validation by targeting the PABPN1 gene transcript.

    abstract::We present a new publicly accessible web-service, RiboSoft, which implements a comprehensive hammerhead ribozyme design procedure. It accepts as input a target sequence (and some design parameters) then generates a set of ranked hammerhead ribozymes, which target the input sequence. This paper describes the implemente...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkv1111

    authors: Kharma N,Varin L,Abu-Baker A,Ouellet J,Najeh S,Ehdaeivand MR,Belmonte G,Ambri A,Rouleau G,Perreault J

    更新日期:2016-02-29 00:00:00

  • Rates of formation and thermal stabilities of RNA:DNA and DNA:DNA duplexes at high concentrations of formamide.

    abstract::The thermal stabilities of RNA:DNA hybrids are substantially greater than those of DNA:DNA duplexes in aqueous electrolyte solutions containing high concentrations of formamide. Association rates to form DNA:DNA duplexes and DNA:RNA hybrids have been measured in these solvents. There is a temperature range in which DN...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/4.5.1539

    authors: Casey J,Davidson N

    更新日期:1977-01-01 00:00:00

  • Integrative analysis of genomic, functional and protein interaction data predicts long-range enhancer-target gene interactions.

    abstract::Multicellular organismal development is controlled by a complex network of transcription factors, promoters and enhancers. Although reliable computational and experimental methods exist for enhancer detection, prediction of their target genes remains a major challenge. On the basis of available literature and ChIP-seq...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkq1081

    authors: Rödelsperger C,Guo G,Kolanczyk M,Pletschacher A,Köhler S,Bauer S,Schulz MH,Robinson PN

    更新日期:2011-04-01 00:00:00

  • Metabolic regulation of apoB mRNA editing is associated with phosphorylation of APOBEC-1 complementation factor.

    abstract::Apolipoprotein B (apoB) mRNA editing is a nuclear event that minimally requires the RNA substrate, APOBEC-1 and APOBEC-1 Complementation Factor (ACF). The co-localization of these macro-molecules within the nucleus and the modulation of hepatic apoB mRNA editing activity have been described following a variety of meta...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkl417

    authors: Lehmann DM,Galloway CA,Sowden MP,Smith HC

    更新日期:2006-07-04 00:00:00

  • Alkemio: association of chemicals with biomedical topics by text and data mining.

    abstract:UNLABELLED:The PubMed® database of biomedical citations allows the retrieval of scientific articles studying the function of chemicals in biology and medicine. Mining millions of available citations to search reported associations between chemicals and topics of interest would require substantial human time. We have im...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gku432

    authors: Gijón-Correas JA,Andrade-Navarro MA,Fontaine JF

    更新日期:2014-07-01 00:00:00

  • Stringent promoter recognition and autoregulation by the group 3 sigma-factor SigF in the cyanobacterium Synechocystis sp. strain PCC 6803.

    abstract::The cyanobacteirum Synechocystis sp. strain PCC 6803 possesses nine species of the sigma (sigma)-factor gene for RNA polymerase (RNAP). Here, we identify and characterize the novel-type promoter recognized by a group 3 sigma-factor, SigF. SigF autoregulates its own transcription and recognizes the promoter of pilA1 th...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn453

    authors: Asayama M,Imamura S

    更新日期:2008-09-01 00:00:00

  • Isolation and partial characterisation of a Chinese hamster O6-alkylguanine-DNA alkyltransferase cDNA.

    abstract::The cDNA encoding Chinese hamster O6-alkylguanine-DNA-alkyltransferase (ATase) has been isolated from a library prepared from RNA isolated from V79 lung fibroblasts which had an upregulated level of this repair activity following stepwise selection with a chloroethylating agent (1, 2). Expression of the cDNA in E. col...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/20.8.1891

    authors: Rafferty JA,Elder RH,Watson AJ,Cawkwell L,Potter PM,Margison GP

    更新日期:1992-04-25 00:00:00

  • Identification and classification of bacterial Type III toxin-antitoxin systems encoded in chromosomal and plasmid genomes.

    abstract::Toxin-antitoxin systems are widespread in bacteria and archaea. They perform diverse functional roles, including the generation of persistence, maintenance of genetic loci and resistance to bacteriophages through abortive infection. Toxin-antitoxin systems have been divided into three types, depending on the nature of...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks231

    authors: Blower TR,Short FL,Rao F,Mizuguchi K,Pei XY,Fineran PC,Luisi BF,Salmond GP

    更新日期:2012-07-01 00:00:00

  • Essential structure of E. coli promoter II. Effect of the sequences around the RNA start point on promoter function.

    abstract::Starting from a synthetic E. coli promoter with the consensus sequences at -35 and -10 regions, a sequence CAT frequently occurred in the RNA start points of natural promoters was introduced in the downstream of the consensus sequences, and the sequences around the RNA start points as well as the relative positions of...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/13.11.4085

    authors: Aoyama T,Takanami M

    更新日期:1985-06-11 00:00:00

  • A chicken middle-repetitive DNA sequence which shares homology with mammalian ubiquitous repeats.

    abstract::We have identified and sequenced two members of a chicken middle repetitive DNA sequence family. By reassociation kinetics, members of this family (termed CRl) are estimated to be present in 1500-7000 copies per chicken haploid genome. The first family member sequenced (CRlUla) is located approximately 2 kb upstream f...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/9.20.5383

    authors: Stumph WE,Kristo P,Tsai MJ,O'Malley BW

    更新日期:1981-10-24 00:00:00