A correlation with exon expression approach to identify cis-regulatory elements for tissue-specific alternative splicing.

Abstract:

:Correlation of motif occurrences with gene expression intensity is an effective strategy for elucidating transcriptional cis-regulatory logic. Here we demonstrate that this approach can also identify cis-regulatory elements for alternative pre-mRNA splicing. Using data from a human exon microarray, we identified 56 cassette exons that exhibited higher transcript-normalized expression in muscle than in other normal adult tissues. Intron sequences flanking these exons were then analyzed to identify candidate regulatory motifs for muscle-specific alternative splicing. Correlation of motif parameters with gene-normalized exon expression levels was examined using linear regression and linear splines on RNA words and degenerate weight matrices, respectively. Our unbiased analysis uncovered multiple candidate regulatory motifs for muscle-specific splicing, many of which are phylogenetically conserved among vertebrate genomes. The most prominent downstream motifs were binding sites for Fox1- and CELF-related splicing factors, and a branchpoint-like element acuaac; pyrimidine-rich elements resembling PTB-binding sites were most significant in upstream introns. Intriguingly, our systematic study indicates a paucity of novel muscle-specific elements that are dominant in short proximal intronic regions. We propose that Fox and CELF proteins play major roles in enforcing the muscle-specific alternative splicing program, facilitating expression of unique isoforms of cytoskeletal proteins critical to muscle cell function.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Das D,Clark TA,Schweitzer A,Yamamoto M,Marr H,Arribere J,Minovitsky S,Poliakov A,Dubchak I,Blume JE,Conboy JG

doi

10.1093/nar/gkm485

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

4845-57

issue

14

eissn

0305-1048

issn

1362-4962

pii

gkm485

journal_volume

35

pub_type

杂志文章
  • SAHG, a comprehensive database of predicted structures of all human proteins.

    abstract::Most proteins from higher organisms are known to be multi-domain proteins and contain substantial numbers of intrinsically disordered (ID) regions. To analyse such protein sequences, those from human for instance, we developed a special protein-structure-prediction pipeline and accumulated the products in the Structur...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkq1057

    authors: Motono C,Nakata J,Koike R,Shimizu K,Shirota M,Amemiya T,Tomii K,Nagano N,Sakaya N,Misoo K,Sato M,Kidera A,Hiroaki H,Shirai T,Kinoshita K,Noguchi T,Ota M

    更新日期:2011-01-01 00:00:00

  • Importance of thiols in the repair mechanisms of DNA containing AP (apurinic or apyrimidinic) sites.

    abstract::Addition of thiol compounds containing an anionic group to the 3'-terminal unsaturated sugar of the 5' fragment obtained from an oligonucleotide containing an AP site cleaved by beta-elimination, can be followed by gel electrophoresis. The technique enables to distinguish between two mechanisms of cleavage of the C3'-...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/16.20.9489

    authors: Bailly V,Verly WG

    更新日期:1988-10-25 00:00:00

  • Genomicus 2018: karyotype evolutionary trees and on-the-fly synteny computing.

    abstract::Since 2010, the Genomicus web server is available online at http://genomicus.biologie.ens.fr/genomicus. This graphical browser provides access to comparative genomic analyses in four different phyla (Vertebrate, Plants, Fungi, and non vertebrate Metazoans). Users can analyse genomic information from extant species, as...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkx1003

    authors: Nguyen NTT,Vincens P,Roest Crollius H,Louis A

    更新日期:2018-01-04 00:00:00

  • Lack of a requirement for strict rotational alignment among transcription factor binding sites in yeast.

    abstract::The MF alpha 1 gene of Saccharomyces cerevisiae is an alpha specific gene whose expression is regulated by two upstream activation sites (UASMF alpha 1S), which are the binding sites for activator proteins, MAT alpha 1 and MCM1. UASMF alpha 1 elements act in a synergistic fashion; lack of either element causes reduced...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/19.11.3099

    authors: Inokuchi K,Nakayama A

    更新日期:1991-06-11 00:00:00

  • A novel regulatory circuit in base excision repair involving AP endonuclease 1, Creb1 and DNA polymerase beta.

    abstract::DNA repair is required to maintain genome stability in stem cells and early embryos. At critical junctures, oxidative damage to DNA requires the base excision repair (BER) pathway. Since early zebrafish embryos lack the major polymerase in BER, DNA polymerase ß, repair proceeds via replicative polymerases, even though...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkq1142

    authors: Pei DS,Yang XJ,Liu W,Guikema JE,Schrader CE,Strauss PR

    更新日期:2011-04-01 00:00:00

  • BSD: the Biodegradative Strain Database.

    abstract::The Biodegradative Strain Database (BSD) is a freely-accessible, web-based database providing detailed information on degradative bacteria and the hazardous substances that they degrade, including corresponding literature citations, relevant patents and links to additional web-based biological and chemical data. The B...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkg032

    authors: Urbance JW,Cole J,Saxman P,Tiedje JM

    更新日期:2003-01-01 00:00:00

  • Differential transcription of the orphan receptor RORbeta in nuclear extracts derived from Neuro2A and HeLa cells.

    abstract::An important model system for studying the process leading to productive transcription is provided by the superfamily of nuclear receptors, which are for the most part ligand-controlled transcription factors. Over the past years several 'orphan' nuclear receptors have been isolated for which no ligand has yet been ide...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/29.16.3424

    authors: Gawlas K,Stunnenberg HG

    更新日期:2001-08-15 00:00:00

  • Effects of pendant groups at phosphorus on binding properties of d-ApA analogues.

    abstract::The interaction of several synthetic analogues of d-ApA with Poly U and Poly dT was examined to explore the effects of substituents at phosphorus on binding properties of oligonucleotides. These analogues contained a bulky, lipophilic group (2,2,2-trichloroethoxy or 2,2,2-trichloro-1,1-dimethylethoxy) a small, uncharg...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/14.8.3487

    authors: Letsinger RL,Bach SA,Eadie JS

    更新日期:1986-04-25 00:00:00

  • High resolution crystal structure of domain I of the Saccharomyces cerevisiae homing endonuclease PI-SceI.

    abstract::The homing endonuclease PI-SceI from Saccharo myces cerevisiae consists of two domains. The protein splicing domain I catalyzes the excision of the mature endonuclease (intein) from a precursor protein and the religation of the flanking amino acid sequences (exteins) to a functional protein. Furthermore, domain I is i...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkf523

    authors: Werner E,Wende W,Pingoud A,Heinemann U

    更新日期:2002-09-15 00:00:00

  • Esc2 promotes telomere stability in response to DNA replication stress.

    abstract::Telomeric regions of the genome are inherently difficult-to-replicate due to their propensity to generate DNA secondary structures and form nucleoprotein complexes that can impede DNA replication fork progression. Precisely how cells respond to DNA replication stalling within a telomere remains poorly characterized, l...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkz158

    authors: Jørgensen SW,Liberti SE,Larsen NB,Lisby M,Mankouri HW,Hickson ID

    更新日期:2019-05-21 00:00:00

  • Conserved elements with potential to form polymorphic G-quadruplex structures in the first intron of human genes.

    abstract::To understand how potential for G-quadruplex formation might influence regulation of gene expression, we examined the 2 kb spanning the transcription start sites (TSS) of the 18 217 human RefSeq genes, distinguishing contributions of template and nontemplate strands. Regions both upstream and downstream of the TSS are...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkm1138

    authors: Eddy J,Maizels N

    更新日期:2008-03-01 00:00:00

  • RegAnalyst: a web interface for the analysis of regulatory motifs, networks and pathways.

    abstract::RegAnalyst is a user-friendly web interface that integrates MoPP (Motif Prediction Program), MyPatternFinder (pattern detection tool) and MycoRegDB (mycobacterial promoter and regulatory elements database). Since motif discovery is a challenging task, numerous tools have been developed over the past few years. Strikin...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkp388

    authors: Sharma D,Mohanty D,Surolia A

    更新日期:2009-07-01 00:00:00

  • The non-autonomous retrotransposon SVA is trans-mobilized by the human LINE-1 protein machinery.

    abstract::SINE-VNTR-Alu (SVA) elements are non-autonomous, hominid-specific non-LTR retrotransposons and distinguished by their organization as composite mobile elements. They represent the evolutionarily youngest, currently active family of human non-LTR retrotransposons, and sporadically generate disease-causing insertions. S...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkr863

    authors: Raiz J,Damert A,Chira S,Held U,Klawitter S,Hamdorf M,Löwer J,Strätling WH,Löwer R,Schumann GG

    更新日期:2012-02-01 00:00:00

  • Golgi-endosome transport mediated by M6PR facilitates release of antisense oligonucleotides from endosomes.

    abstract::Release of phosphorothioate antisense oligonucleotides (PS-ASOs) from late endosomes (LEs) is a rate-limiting step and a poorly defined process for productive intracellular ASO drug delivery. Here, we examined the role of Golgi-endosome transport, specifically M6PR shuttling mediated by GCC2, in PS-ASO trafficking and...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkz1171

    authors: Liang XH,Sun H,Hsu CW,Nichols JG,Vickers TA,De Hoyos CL,Crooke ST

    更新日期:2020-02-20 00:00:00

  • JSNP: a database of common gene variations in the Japanese population.

    abstract::JSNP is a repository of Japanese Single Nucleotide Polymorphism (SNP) data, begun in 2000 and developed through the Prime Minister's Millennium Project. The aim of this undertaking is to identify and collate up to 150 000 SNPs from the Japanese population, located in genes or in adjacent regions that might influence t...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/30.1.158

    authors: Hirakawa M,Tanaka T,Hashimoto Y,Kuroda M,Takagi T,Nakamura Y

    更新日期:2002-01-01 00:00:00

  • Asn-tRNA in Lactobacillus bulgaricus is formed by asparaginylation of tRNA and not by transamidation of Asp-tRNA.

    abstract::In many organisms (e.g., gram-positive eubacteria) Gin-tRNA is not formed by direct glutaminylation of tRNAGln but by a specific transamidation of Glu-tRNAGln. We wondered whether a similar transamidation pathway also operates in the formation of Asn-tRNA in these organisms. Therefore we tested in S-100 preparations o...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/24.14.2648

    authors: Kim SI,Nalaskowska M,Germond JE,Pridmore D,Söll D

    更新日期:1996-07-15 00:00:00

  • Rapid, modular and reliable construction of complex mammalian gene circuits.

    abstract::We developed a framework for quick and reliable construction of complex gene circuits for genetically engineering mammalian cells. Our hierarchical framework is based on a novel nucleotide addressing system for defining the position of each part in an overall circuit. With this framework, we demonstrate construction o...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkt605

    authors: Guye P,Li Y,Wroblewska L,Duportet X,Weiss R

    更新日期:2013-09-01 00:00:00

  • The influence of tertiary structural restraints on conformational transitions in superhelical DNA.

    abstract::This paper examines theoretically the effects that restraints on the tertiary structure of a superhelical DNA domain exert on the energetics of linking and the onset of conformational transitions. The most important tertiary constraint arises from the nucleosomal winding of genomic DNA in vivo. Conformational transiti...

    journal_title:Nucleic acids research

    pub_type: 杂志文章,评审

    doi:10.1093/nar/15.23.9985

    authors: Benham CJ

    更新日期:1987-12-10 00:00:00

  • Roles of cis-acting elements and chromatin structure in Drosophila alcohol dehydrogenase gene expression.

    abstract::The alcohol dehydrogenase (Adh) gene of D. melanogaster is transcribed from two different promoters during fly development: the distal (adult) and the proximal (embryonic-larval). Certain aspects of Adh gene regulation are represented in Drosophila continuous cell lines. We have used Drosophila tissue culture cells in...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/15.19.7903

    authors: Benyajati C,Ayer S,McKeon J,Ewel A,Huang J

    更新日期:1987-10-12 00:00:00

  • Two types of triplicated alpha-globin loci in humans.

    abstract::DNA from healthy Malaysian newborns was studied on gene maps after digestion with different restriction endonucleases. Of 65 newborns, two were found to be carriers of two different variants of triplicated alpha-globin loci. In variant no. 1, found in an Malay, the three alpha-globin genes are in an elongated DNA frag...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/9.15.3707

    authors: Lie-Injo LE,Herrera AR,Kan YW

    更新日期:1981-08-11 00:00:00

  • Analysis of neonatal brain lacking ATRX or MeCP2 reveals changes in nucleosome density, CTCF binding and chromatin looping.

    abstract::ATRX and MeCP2 belong to an expanding group of chromatin-associated proteins implicated in human neurodevelopmental disorders, although their gene-regulatory activities are not fully resolved. Loss of ATRX prevents full repression of an imprinted gene network in the postnatal brain and in this study we address the mec...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gku564

    authors: Kernohan KD,Vernimmen D,Gloor GB,Bérubé NG

    更新日期:2014-07-01 00:00:00

  • Differential activation of DNA-PK based on DNA strand orientation and sequence bias.

    abstract::DNA-PKcs and Ku are essential components of the complex that catalyzes non-homologous end joining (NHEJ) of DNA double-strand breaks (DSBs). Ku, a heterodimeric protein, binds to DNA ends and facilitates recruitment of the catalytic subunit, DNA-PKcs. We have investigated the effect of DNA strand orientation and seque...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gki157

    authors: Pawelczak KS,Andrews BJ,Turchi JJ

    更新日期:2005-01-07 00:00:00

  • Rapid assay for detection of Escherichia coli xanthine-guanine phosphoribosyltransferase activity in transduced cells.

    abstract::Cultured mammalian cells transduced with the Escherichia coli gene, Ecogpt, synthesize the bacterial enzyme xanthine-guanine phosphoribosyl transferase (XGPT) (1). This paper describes a method for measuring XGPT activity in crude cell extracts by following the conversion of 14C-xanthine (X) to 14C-xanthine monophosph...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/13.8.2921

    authors: Chu G,Berg P

    更新日期:1985-04-25 00:00:00

  • ATPase activity of the UvrA and UvrAB protein complexes of the Escherichia coli UvrABC endonuclease.

    abstract::We have analyzed the ATPase activity exhibited by the UvrABC DNA repair complex. The UvrA protein is an ATPase whose lack of DNA dependence may be related to the ATP induced monomer-dimer transitions. ATP induced dimerization may be responsible for the enhanced DNA binding activity observed in the presence of ATP. Alt...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/17.11.4145

    authors: Oh EY,Claassen L,Thiagalingam S,Mazur S,Grossman L

    更新日期:1989-06-12 00:00:00

  • Characterization and purification of Adh distal promoter factor 2, Adf-2, a cell-specific and promoter-specific repressor in Drosophila.

    abstract::Chromatin footprinting in Drosophila tissue culture cells has detected the binding of a non-histone protein at +8 of the distal Adh RNA start site, on a 10-bp direct repeat motif abutting a nucleosome positioned over the inactive Adh distal promoter. Alternatively the active promoter is bound by a transcription initia...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/20.17.4481

    authors: Benyajati C,Ewel A,McKeon J,Chovav M,Juan E

    更新日期:1992-09-11 00:00:00

  • A method of one-step enzyme labelling of short oligonucleotide probes for filter hybridisation.

    abstract::Here we describe a method of labelling short oligonucleotide probes with enzyme without purification or chemical modifications. Biotinylated oligonucleotides as short as 10 nt are coupled with streptavidin-conjugated enzyme, hybridised and detected with enzyme-triggered chemiluminescence. The detection of hybridisatio...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/27.2.703

    authors: Guerasimova A,Ivanov I,Lehrach H

    更新日期:1999-01-15 00:00:00

  • Thermodynamically stable and genetically unstable G-quadruplexes are depleted in genomes across species.

    abstract::G-quadruplexes play various roles in multiple biological processes, which can be positive when a G4 is involved in the regulation of gene expression or detrimental when the folding of a stable G4 impairs DNA replication promoting genome instability. This duality interrogates the significance of their presence within g...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkz463

    authors: Puig Lombardi E,Holmes A,Verga D,Teulade-Fichou MP,Nicolas A,Londoño-Vallejo A

    更新日期:2019-07-09 00:00:00

  • Signal structure for transcriptional activation in the upstream regions of virulence genes on the hairy-root-inducing plasmid A4.

    abstract::The inducibility of the vir genes (virA, -B, -C, -D, -E, and -G) on pRiA4 was examined at the transcriptional level, and the RNA-starting sites were determined by S1-nuclease mapping and primer-extension experiments. All of these genes were inducible, while virA, -E, and -G were transcribed even under noninducing cond...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/17.21.8711

    authors: Aoyama T,Takanami M,Oka A

    更新日期:1989-11-11 00:00:00

  • Pseudogenes for human U2 small nuclear RNA do not have a fixed site of 3' truncation.

    abstract::We present the sequences of five additional human U2 pseudogenes which are very similar to the U2.13 pseudogene reported previously [Van Arsdell et al. (1981) Cell 26, 11-17]. All six U2 pseudogenes preserve the 5' end of the mature U2 snRNA sequence, and all six are flanked by nearly perfect direct repeats that diffe...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/12.3.1463

    authors: Van Arsdell SW,Weiner AM

    更新日期:1984-02-10 00:00:00

  • Amino acid sequence variations in Nicotiana CRR4 orthologs determine the species-specific efficiency of RNA editing in plastids.

    abstract::In flowering plants, RNA editing is a posttranscriptional process that converts specific C to U in organelle mRNAs. Nicotiana tabacum is an allotetraploid species derived from the progenitors of Nicotiana sylvestris and Nicotiana tomentosiformis. These Nicotiana species have been used as a model for understanding the ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn629

    authors: Okuda K,Habata Y,Kobayashi Y,Shikanai T

    更新日期:2008-11-01 00:00:00