The high mobility group A2 protein epigenetically silences the Cdh1 gene during epithelial-to-mesenchymal transition.


: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.


Nucleic Acids Res


Nucleic acids research


Tan EJ,Kahata K,Idås O,Thuault S,Heldin CH,Moustakas A




Has Abstract


2015-01-01 00:00:00














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    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: Gegenheimer P

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  • Mycobacterium tuberculosis 6C sRNA binds multiple mRNA targets via C-rich loops independent of RNA chaperones.

    abstract::Bacterial small regulatory RNAs (sRNAs) are the most abundant class of post-transcriptional regulators and have been well studied in Gram-negative bacteria. Little is known about the functions and mechanisms of sRNAs in high GC Gram-positive bacteria including Mycobacterium and Streptomyces. Here, we performed an in-d...

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    authors: Mai J,Rao C,Watt J,Sun X,Lin C,Zhang L,Liu J

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  • The interaction of DNA-targeted platinum phenanthridinium complexes with DNA.

    abstract::Cisplatin analogues were synthesised that consisted of platinum(II) diamine complexes tethered via a polymethylene chain ( n = 3, 5, 8 and 10) to a phenanthridinium cation. Both chloro and iodo leaving groups were examined. DNA adduct formation was quantitatively analysed using a linear amplification system with the p...

    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: Whittaker J,McFadyen WD,Wickham G,Wakelin LP,Murray V

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  • BMI1 is a target gene of E2F-1 and is strongly expressed in primary neuroblastomas.

    abstract::The oncogene BMI1 encodes a polycomb group transcription factor that is required for embryonic development and self-renewal of stem cells. Despite these important functions little is known about the regulation of BMI1 expression. A cDNA microarray based search for target genes of E2F-1 in neuroblastoma cells expressin...

    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: Nowak K,Kerl K,Fehr D,Kramps C,Gessner C,Killmer K,Samans B,Berwanger B,Christiansen H,Lutz W

    更新日期:2006-03-31 00:00:00

  • EGF-induced jun B-expression in transfected P19 embryonal carcinoma cells expressing EGF-receptors is dependent on Jun D.

    abstract::The TPA-inducible transcription factor AP-1, consisting of homo- or hetero-dimers of members of the Jun- and Fos-families, regulates transcription of a wide variety of genes containing the TPA response element (TRE). In P19 embryonal carcinoma (EC) cells, Jun D is the only component of AP-1 expressed, while in these c...

    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: den Hertog J,de Groot RP,de Laat SW,Kruijer W

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  • Repeated DNA sequences in fungi.

    abstract::Several fungal species, representatives of all broad groups like basidiomycetes, ascomycetes and phycomycetes, were examined for the nature of repeated DNA sequences by DNA:DNA reassociation studies using hydroxyapatite chromatography. All of the fungal species tested contained 10-20% repeated DNA sequences. There are...

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    pub_type: 杂志文章


    authors: Dutta SK

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  • Evidence that the Upf1-related molecular motor scans the 3'-UTR to ensure mRNA integrity.

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    pub_type: 杂志文章


    authors: Shigeoka T,Kato S,Kawaichi M,Ishida Y

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  • Transcription regulation of caspase-1 by R393 of HIPPI and its molecular partner HIP-1.

    abstract::Earlier we have shown that exogenous expression of HIPPI, a molecular partner of Huntingtin interacting protein HIP-1, induces apoptosis and increases expression of caspases-1, -8 and -10 in HeLa and Neuro2A cells. The C-terminal pseudo death effector domain of HIPPI (pDED-HIPPI) specifically interacts with the putati...

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    authors: Banerjee M,Datta M,Majumder P,Mukhopadhyay D,Bhattacharyya NP

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  • Multiply damaged sites in DNA: interactions with Escherichia coli endonucleases III and VIII.

    abstract::Bursts of free radicals produced by ionization of water in close vicinity to DNA can produce clusters of opposed DNA lesions and these are termed multiply damaged sites (MDS). How MDS are processed by the Escherichia coli DNA glycosylases, endonuclease (endo) III and endo VIII, which recognize oxidized pyrimidines, is...

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    authors: Harrison L,Hatahet Z,Purmal AA,Wallace SS

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  • Linker phosphoramidite reagents for the attachment of the first nucleoside to underivatized solid-phase supports.

    abstract::New linker phosphoramidite reagents containing a cleavable 3'-ester linkage are used for attaching the first nucleoside to the surface of a solid- phase support. Inexpensive, underivatized amino supports, such as long chain alkylamine controlled-pore glass, can serve as universal supports. No modifications to phosphor...

    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: Pon RT,Yu S

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  • Immunological and spectroscopic studies of poly(dG-dC).poly(dG-dC) modified by cis-diamminedichloroplatinum(II).

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    pub_type: 杂志文章


    authors: Malinge JM,Ptak M,Leng M

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  • Sequence search on a supercomputer.

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    authors: Gotoh O,Tagashira Y

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  • The crystal structure of the DNA-binding domain of vIRF-1 from the oncogenic KSHV reveals a conserved fold for DNA binding and reinforces its role as a transcription factor.

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    authors: Hew K,Dahlroth SL,Venkatachalam R,Nasertorabi F,Lim BT,Cornvik T,Nordlund P

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  • Anisotropic overall and internal motions of short DNA fragments.

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    authors: Härd T,Kearns DR

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  • Characterization of highly and moderately repetitive 500 bp Eco RI fragments from Xenopus laevis DNA.

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    authors: Hummel S,Meyerhof W,Korge E,Knöchel W

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  • An insulinoma nuclear factor binding to GGGCCC motifs in human insulin gene.

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    authors: Reibel L,Besnard C,Lores P,Jami J,Gacon G

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  • Molecular characteristics of reiterative DNA unwinding by the Caenorhabditis elegans RecQ helicase.

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    authors: Choi S,Lee SW,Kim H,Ahn B

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  • The salt dependence of DNA recognition by NF-kappaB p50: a detailed kinetic analysis of the effects on affinityand specificity.

    abstract::The binding kinetics of NF-kappaB p50 to the Ig-kappaB site and to a DNA duplex with no specific binding site were determined under varying conditions of potassium chloride concentration using a surface plasmonresonance biosensor. Association and dissociation rate constants were measured enabling calculation of the di...

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    authors: Hart DJ,Speight RE,Cooper MA,Sutherland JD,Blackburn JM

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  • Recognition of distinct HLA-DQA1 promoter elements by a single nuclear factor containing Jun and Fos or antigenically related proteins.

    abstract::The activity of MHC class II promoters depends upon conserved regulatory signals one of which, the extended X-box, contains in its X2 subregion a sequence related to the cAMP response element, CRE and to the TPA response element, TRE. Accordingly, X2 is recognized by the AP-1 factor and by other c-Jun or c-Fos contain...

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    pub_type: 杂志文章


    authors: Neve Ombra M,Autiero M,DeLerma Barbaro A,Barretta R,Del Pozzo G,Guardiola J

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  • liqDB: a small-RNAseq knowledge discovery database for liquid biopsy studies.

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    authors: Aparicio-Puerta E,Jáspez D,Lebrón R,Koppers-Lalic D,Marchal JA,Hackenberg M

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  • Processing of complementary sense RNAs of Digitaria streak virus in its host and in transgenic tobacco.

    abstract::We have used a polymerase chain reaction (PCR) procedure to analyse low abundance complementary sense RNAs of Digitaria streak virus (DSV) from infected leaves of Digitaria setigera. This study has confirmed that both spliced and unspliced RNAs are synthesised by the same transcription unit. The position of the intron...

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    authors: Mullineaux PM,Guerineau F,Accotto GP

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  • One-pot DNA construction for synthetic biology: the Modular Overlap-Directed Assembly with Linkers (MODAL) strategy.

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    authors: Casini A,MacDonald JT,De Jonghe J,Christodoulou G,Freemont PS,Baldwin GS,Ellis T

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    journal_title:Nucleic acids research

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    authors: Tan W,Zolotukhin AS,Tretyakova I,Bear J,Lindtner S,Smulevitch SV,Felber BK

    更新日期:2005-07-13 00:00:00

  • Phospho3D 2.0: an enhanced database of three-dimensional structures of phosphorylation sites.

    abstract::Phospho3D is a database of three-dimensional (3D) structures of phosphorylation sites (P-sites) derived from the Phospho.ELM database, which also collects information on the residues surrounding the P-site in space (3D zones). The database also provides the results of a large-scale structural comparison of the 3D zone...

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    authors: Zanzoni A,Carbajo D,Diella F,Gherardini PF,Tramontano A,Helmer-Citterich M,Via A

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    abstract::The specific recognition of homopurine-homo pyrimidine regions in duplex DNA by triplex-forming oligonucleotides (TFOs) provides an attractive strategy for genetic manipulation. Alkylation of nucleobases with functionalized TFOs would have the potential for site-directed mutagenesis. Recently, we demonstrated that a T...

    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: Nagatsugi F,Sasaki S,Miller PS,Seidman MM

    更新日期:2003-03-15 00:00:00

  • RepD-mediated recruitment of PcrA helicase at the Staphylococcus aureus pC221 plasmid replication origin, oriD.

    abstract::Plasmid encoded replication initiation (Rep) proteins recruit host helicases to plasmid replication origins. Previously, we showed that RepD recruits directionally the PcrA helicase to the pC221 oriD, remains associated with it, and increases its processivity during plasmid unwinding. Here we show that RepD forms a co...

    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: Machón C,Lynch GP,Thomson NH,Scott DJ,Thomas CD,Soultanas P

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  • Correlation between sequence conservation and the genomic context after gene duplication.

    abstract::A key complication in comparative genomics for reliable gene function prediction is the existence of duplicated genes. To study the effect of gene duplication on function prediction, we analyze orthologs between pairs of genomes where in one genome the orthologous gene has duplicated after the speciation of the two ge...

    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: Notebaart RA,Huynen MA,Teusink B,Siezen RJ,Snel B

    更新日期:2005-10-27 00:00:00

  • AVPpred: collection and prediction of highly effective antiviral peptides.

    abstract::In the battle against viruses, antiviral peptides (AVPs) had demonstrated the immense potential. Presently, more than 15 peptide-based drugs are in various stages of clinical trials. Emerging and re-emerging viruses further emphasize the efforts to accelerate antiviral drug discovery efforts. Despite, huge importance ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: Thakur N,Qureshi A,Kumar M

    更新日期:2012-07-01 00:00:00

  • Stabilization of XIAP mRNA through the RNA binding protein HuR regulated by cellular polyamines.

    abstract::The X chromosome-linked inhibitor of apoptosis protein (XIAP) is the most potent intrinsic caspase inhibitor and plays an important role in the maintenance of intestinal epithelial integrity. The RNA binding protein, HuR, regulates the stability and translation of many target transcripts. Here, we report that HuR asso...

    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: Zhang X,Zou T,Rao JN,Liu L,Xiao L,Wang PY,Cui YH,Gorospe M,Wang JY

    更新日期:2009-12-01 00:00:00

  • The crystal structure of the RNA/DNA hybrid r(GAAGAGAAGC). d(GCTTCTCTTC) shows significant differences to that found in solution.

    abstract::The crystal structure of the RNA/DNA hybrid r(GAAGAGAAGC). d(GCTTCTCTTC) has been solved and refined at 2.5 A resolution. The refinement procedure converged at R = 0.181 for all reflections in the range 20.0-2.5 A. In the crystal, the RNA/DNA hybrid duplex has an A' conformation with all but one of the nucleotide suga...

    journal_title:Nucleic acids research

    pub_type: 杂志文章


    authors: Conn GL,Brown T,Leonard GA

    更新日期:1999-01-15 00:00:00