Abstract:
:The loss of the tumour suppressor E-cadherin (Cdh1) is a key event during tumourigenesis and epithelial-mesenchymal transition (EMT). Transforming growth factor-β (TGFβ) triggers EMT by inducing the expression of non-histone chromatin protein High Mobility Group A2 (HMGA2). We have previously shown that HMGA2, together with Smads, regulate a network of EMT-transcription factors (EMT-TFs) like Snail1, Snail2, ZEB1, ZEB2 and Twist1, most of which are well-known repressors of the Cdh1 gene. In this study, we show that the Cdh1 promoter is hypermethylated and epigenetically silenced in our constitutive EMT cell model, whereby HMGA2 is ectopically expressed in mammary epithelial NMuMG cells and these cells are highly motile and invasive. Furthermore, HMGA2 remodels the chromatin to favour binding of de novo DNA methyltransferase 3A (DNMT3A) to the Cdh1 promoter. E-cadherin expression could be restored after treatment with the DNA de-methylating agent 5-aza-2'-deoxycytidine. Here, we describe a new epigenetic role for HMGA2, which follows the actions that HMGA2 initiates via the EMT-TFs, thus achieving sustained silencing of E-cadherin expression and promoting tumour cell invasion.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Tan EJ,Kahata K,Idås O,Thuault S,Heldin CH,Moustakas Adoi
10.1093/nar/gku1293subject
Has Abstractpub_date
2015-01-01 00:00:00pages
162-78issue
1eissn
0305-1048issn
1362-4962pii
gku1293journal_volume
43pub_type
杂志文章abstract::SRS (Sequence Retrieval System) is a widely used keyword search engine for querying biological databases. BLAST2 is the most widely used tool to query databases by sequence similarity search. These tools allow users to retrieve sequences by shared keyword or by shared similarity, with many public web servers available...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg535
更新日期:2003-07-01 00:00:00
abstract::Directed molecular evolution and combinatorial methodologies are playing an increasingly important role in the field of protein engineering. The general approach of generating a library of partially randomized genes, expressing the gene library to generate the proteins the library encodes and then screening the protei...
journal_title:Nucleic acids research
pub_type: 杂志文章,评审
doi:10.1093/nar/gkh315
更新日期:2004-02-27 00:00:00
abstract::TAP/hNXF1 is a key factor that mediates general cellular mRNA export from the nucleus, and its orthologs are structurally and functionally conserved from yeast to humans. Metazoans encode additional proteins that share homology and domain organization with TAP/hNXF1, suggesting their participation in mRNA metabolism; ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki706
更新日期:2005-07-13 00:00:00
abstract::Large-scale cooperative helix opening has been previously observed in A + T rich sequences contained in supercoiled DNA molecules at elevated temperatures. Since it is well known that helix melting of linear DNA is suppressed by addition of salt, we have investigated the effects of added salts on opening transitions i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.11.2042
更新日期:1994-06-11 00:00:00
abstract::Constitutive expression of major histocompatibility complex class II (MHC II) antigens normally occurs in B-lymphocytes and antigen presenting cells of the monocyte/macrophage lineage. However, many malignant tumours and transformed cells express these proteins aberrantly. We demonstrate here that the MHC II DR alpha ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/20.18.4881
更新日期:1992-09-25 00:00:00
abstract::The effects of the treatment of cultured human and simian cells with Cadmium (Cd), a toxic and carcinogenic metal, were first assayed on macromolecular synthesis. It was observed that DNA synthesis was inhibited by Cd concentrations considerably lower than those inhibiting protein and RNA synthesis. Because of the nec...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.10.4211
更新日期:1987-05-26 00:00:00
abstract::At the DNA/RNA level, biological signals are defined by a combination of spatial structures and sequence motifs. Until now, few attempts had been made in writing general purpose search programs that take into account both sequence and structure criteria. Indeed, the most successful structure scanning programs are usua...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.8.1395
更新日期:1996-04-15 00:00:00
abstract::The high-mobility-group A2 protein (HMGA2) plays important functional roles in transcriptional regulation, DNA replication and chromatin structure. In this study, the effect of histone deacetylase inhibition on the transcriptional activity of the Hmga2 gene was investigated in vivo both at the endogenous gene level an...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg403
更新日期:2003-06-15 00:00:00
abstract::Transcriptional repression of pathogen defense-related genes is essential for plant growth and development. Several proteins are known to be involved in the transcriptional regulation of plant defense responses. However, mechanisms by which expression of defense-related genes are regulated by repressor proteins are po...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks683
更新日期:2012-10-01 00:00:00
abstract::A detailed scheme of the Peptidyl Transferase Centre of bacterial ribosomes is proposed by summarizing the literature data on the substrate specificity of the acceptor and donor sites. According to the proposed scheme only the elements of the donor and acceptor having a stable structure bind with the ribosome. The pre...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/2.12.2223
更新日期:1975-12-01 00:00:00
abstract::Apicoplast, an essential organelle of human malaria parasite Plasmodium falciparum contains a ∼35 kb circular genome and is a possible target for therapy. Proteins required for the replication and maintenance of the apicoplast DNA are not clearly known. Here we report the presence of single-stranded DNA binding protei...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq565
更新日期:2010-11-01 00:00:00
abstract::Microbial biosynthetic gene clusters are a valuable source of bioactive molecules. However, because they typically represent a small fraction of genomic material in most metagenomic samples, it remains challenging to deeply sequence them. We present an approach to isolate and sequence gene clusters in metagenomic samp...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa131
更新日期:2020-05-07 00:00:00
abstract::Bgee is a database to retrieve and compare gene expression patterns in multiple animal species, produced by integrating multiple data types (RNA-Seq, Affymetrix, in situ hybridization, and EST data). It is based exclusively on curated healthy wild-type expression data (e.g., no gene knock-out, no treatment, no disease...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa793
更新日期:2021-01-08 00:00:00
abstract::Expansions of (GAA)n repeats within the first intron of the frataxin gene reduce its expression, resulting in a hereditary neurodegenerative disorder, Friedreich's ataxia. While it is generally believed that expanded (GAA)n repeats block transcription elongation, fine mechanisms responsible for gene repression are not...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl1140
更新日期:2007-01-01 00:00:00
abstract::It is a routine task in metabolic engineering to introduce multicomponent pathways into a heterologous host for production of metabolites. However, this process sometimes may take weeks to months due to the lack of standardized genetic tools. Here, we present a method for the design and construction of biological part...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv464
更新日期:2015-07-27 00:00:00
abstract::The rDNA cluster in Saccharomyces cerevisiae is located 450 kb from the left end and 610 kb from the right end of chromosome XII and consists of approximately 150 tandemly repeated copies of a 9.1 kb rDNA unit. To explore the biological significance of this specific chromosomal context, chromosome XII was split at bot...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl293
更新日期:2006-05-31 00:00:00
abstract::Developmental stage-specific expression of the β-type globin genes is regulated by many cis- and trans-acting components. The adult β-globin gene contains an E-box located 60 bp downstream of the transcription start site that has been shown to bind transcription factor upstream stimulatory factor (USF) and to contribu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gku107
更新日期:2014-04-01 00:00:00
abstract::The replication origin (oriC) of the Escherichia coli chromosome has been cloned and the region essential for chromosomal replication has been delimited to 245 base pairs. In previous studies the ability of recombinants between oriC and ColE1-type vectors, to transform E. coli polA- strains was used to determine which...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/11.22.8007
更新日期:1983-11-25 00:00:00
abstract::RNA polymerase III recognizes and pauses at its terminator, an oligo(dT) tract in non-template DNA, terminates 3' oligo(rU) synthesis within this sequence, and releases the RNA. The pol III subunit Rpc11p (C11) mediates RNA 3'-5' cleavage in the catalytic center of pol III during pausing. The amino and carboxyl region...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr182
更新日期:2011-08-01 00:00:00
abstract::We describe Protogene, a server that can turn a protein multiple sequence alignment into the equivalent alignment of the original gene coding DNA. Protogene relies on a pipeline where every initial protein sequence is BLASTed against RefSeq or NR. The annotation associated with potential matches is used to identify th...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl170
更新日期:2006-07-01 00:00:00
abstract::Homologous recombination (HR) is important in repairing errors of replication and other forms of DNA damage. In mammalian cells, potential templates include the homologous chromosome, and after DNA replication, the sister chromatid. Previous work has shown that the mammalian recombination machinery is organized to sup...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh280
更新日期:2004-02-20 00:00:00
abstract::5' Terminal cap structures of hnRNA have been characterized and the extent of capping determined as a function of embryonic development. Sea urchin embryo hnRNA contains only the type-1 cap, m7GpppNmpNp, with the type-2 cap, which has a 2'-0-methylated subpenultimate nucleotide, being associated only with stable small...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/6.6.2307
更新日期:1979-01-01 00:00:00
abstract::In this study, we demonstrate that the lack of retinoic acid-related orphan receptor (ROR) γ or α expression in mice significantly reduced the peak expression level of Cry1, Bmal1, E4bp4, Rev-Erbα and Per2 in an ROR isotype- and tissue-selective manner without affecting the phase of their rhythmic expression. Analysis...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks630
更新日期:2012-09-01 00:00:00
abstract::The stable intermediates formed in the reaction of cytosine, cytidine and adenosine with chloracetaldehyde were isolated. The -CH2CH/OH/- bridge between the exo and endo nitrogen atoms of the parent base was found in these compounds by means of PMR spectroscopy. Their acid-induced dehydration resulted in formation of ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/5.3.789
更新日期:1978-03-01 00:00:00
abstract::The transcriptional promoter of satellite 2 from the eastern newt, Notophthalmus viridescens, was analyzed by assaying the activity of deleted or mutated satellite 2 clones in Xenopus laevis oocytes. Two elements in the promoter were found to be important for transcription. These elements have sequences that are simil...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/22.22.4697
更新日期:1994-11-11 00:00:00
abstract::The nucleotide sequence of the celD gene, encoding the previously crystallized endoglucanase D of Clostridium thermocellum, is reported. The enzyme shares a conserved, reiterated domain with the COOH-terminal end of endoglucanases A and B from the same organism. The overexpression in Escherichia coli of celD subcloned...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.21.8605
更新日期:1986-11-11 00:00:00
abstract::Genome organization into transcriptionally active domains denotes one of the first levels of gene expression regulation. Although the chromatin domain concept is generally accepted, only little is known on how domain organization impacts the regulation of differential gene expression. Insulators might hold answers to ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq740
更新日期:2011-01-01 00:00:00
abstract::Type III restriction enzymes have been demonstrated to require two unmethylated asymmetric recognition sites oriented head-to-head to elicit double-strand break 25-27 bp downstream of one of the two sites. The proposed DNA cleavage mechanism involves ATP-dependent DNA translocation. The sequence context of the recogni...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh899
更新日期:2004-10-22 00:00:00
abstract::A physical map is presented for the 1200 kb genome of Mycoplasma mycoides subsp. mycoides Y, locating 32 cleavage sites for 8 restriction endonucleases. The large restriction fragments involved were separated and sized by pulsed-field agarose gel electrophoresis. Their locations on the map were determined by probing S...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.13.6027
更新日期:1988-07-11 00:00:00
abstract::RNA editing by adensosine deaminases is a widespread mechanism to alter genetic information in metazoa. In addition to modifications in non-coding regions, editing contributes to diversification of protein function, in analogy to alternative splicing. However, although splicing programs respond to external signals, fa...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1045
更新日期:2013-01-01 00:00:00