Binding of 14-3-3 reader proteins to phosphorylated DNMT1 facilitates aberrant DNA methylation and gene expression.

Abstract:

:Mammalian DNA (cytosine-5) methyltransferase 1 (DNMT1) is essential for maintenance methylation. Phosphorylation of Ser143 (pSer143) stabilizes DNMT1 during DNA replication. Here, we show 14-3-3 is a reader protein of DNMT1pSer143. In mammalian cells 14-3-3 colocalizes and binds DNMT1pSer143 post-DNA replication. The level of DNMT1pSer143 increased with overexpression of 14-3-3 and decreased by its depletion. Binding of 14-3-3 proteins with DNMT1pSer143 resulted in inhibition of DNA methylation activity in vitro. In addition, overexpression of 14-3-3 in NIH3T3 cells led to decrease in DNMT1 specific activity resulting in hypomethylation of the genome that was rescued by transfection of DNMT1. Genes representing cell migration, mobility, proliferation and focal adhesion pathway were hypomethylated and overexpressed. Furthermore, overexpression of 14-3-3 also resulted in enhanced cell invasion. Analysis of TCGA breast cancer patient data showed significant correlation for DNA hypomethylation and reduced patient survival with increased 14-3-3 expressions. Therefore, we suggest that 14-3-3 is a crucial reader of DNMT1pSer143 that regulates DNA methylation and altered gene expression that contributes to cell invasion.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Estève PO,Zhang G,Ponnaluri VK,Deepti K,Chin HG,Dai N,Sagum C,Black K,Corrêa IR Jr,Bedford MT,Cheng X,Pradhan S

doi

10.1093/nar/gkv1162

subject

Has Abstract

pub_date

2016-02-29 00:00:00

pages

1642-56

issue

4

eissn

0305-1048

issn

1362-4962

pii

gkv1162

journal_volume

44

pub_type

杂志文章
  • A variable tandem repeat locus mapped to chromosome band 10q26 is amplified and rearranged in leukocyte DNAs of two cancer patients.

    abstract::A highly polymorphic locus associated with the variable tandem repetition of a 35 bp consensus sequence was mapped to chromosome 10, band q26. Examination of leukocyte DNA from a cancer patient revealed the twenty-fold amplification of one allelic fragment of this locus, while the other allelic fragment demonstrated a...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/14.20.7929

    authors: Colb M,Yang-Feng T,Francke U,Mermer B,Parkinson DR,Krontiris TG

    更新日期:1986-10-24 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

    doi:10.1093/nar/27.2.555

    authors: Conn GL,Brown T,Leonard GA

    更新日期:1999-01-15 00:00:00

  • TcSNP: a database of genetic variation in Trypanosoma cruzi.

    abstract::The TcSNP database (http://snps.tcruzi.org) integrates information on genetic variation (polymorphisms and mutations) for different stocks, strains and isolates of Trypanosoma cruzi, the causative agent of Chagas disease. The database incorporates sequences (genes from the T. cruzi reference genome, mRNAs, ESTs and ge...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkn874

    authors: Ackermann AA,Carmona SJ,Agüero F

    更新日期:2009-01-01 00:00:00

  • Interaction of N-acetyl-phenylalanyl-tRNAPhe with 70S ribosomes of Escherichia coli.

    abstract::The interaction of N--Acetyl--Phe--tRNA Phe with 70 S ribosomes is a reversible process in the absence as well as in the presence of messenger. The equilibrium binding constants of these interactions were measured at different magnesium concentrations and temperatures and thermodynamical quantities computed. The entha...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/5.10.3871

    authors: Odinzov VB,Kirillov SV

    更新日期:1978-10-01 00:00:00

  • MAZ induces MYB expression during the exit from quiescence via the E2F site in the MYB promoter.

    abstract::Most E2F-binding sites repress transcription through the recruitment of Retinoblastoma (RB) family members until the end of the G1 cell-cycle phase. Although the MYB promoter contains an E2F-binding site, its transcription is activated shortly after the exit from quiescence, before RB family members inactivation, by u...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkx641

    authors: Álvaro-Blanco J,Urso K,Chiodo Y,Martín-Cortázar C,Kourani O,Arco PG,Rodríguez-Martínez M,Calonge E,Alcamí J,Redondo JM,Iglesias T,Campanero MR

    更新日期:2017-09-29 00:00:00

  • p73 competes with p53 and attenuates its response in a human ovarian cancer cell line.

    abstract::The transcriptional activity of the p53 tumor suppressor protein is crucial for the regulation of cell growth, apoptosis and tumor progression. The first identified p53 relative, p73, was reported to be monoallelically expressed in normal tissues. In some tumors, loss of heterozygosity was associated with overexpressi...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/28.2.513

    authors: Vikhanskaya F,D'Incalci M,Broggini M

    更新日期:2000-01-15 00:00:00

  • A transgenic mouse that expresses a diversity of human sequence heavy and light chain immunoglobulins.

    abstract::We have generated transgenic mice that express a diverse repertoire of human sequence immunoglobulins. The expression of this repertoire is directed by light and heavy chain minilocus transgenes comprised of human protein coding sequences in an unrearranged, germ-line configuration. In this paper we describe the const...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/20.23.6287

    authors: Taylor LD,Carmack CE,Schramm SR,Mashayekh R,Higgins KM,Kuo CC,Woodhouse C,Kay RM,Lonberg N

    更新日期:1992-12-11 00:00:00

  • Single locus microsatellites isolated using 5' anchored PCR.

    abstract::Microsatellites are widely used as genetic markers because they are co-dominant, multiallelic, easily scored and highly polymorphic. A major drawback of microsatellite markers is the time and cost required to characterise them. We have developed a novel technique to reduce this cost by producing a microsatellite-rich ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/24.21.4369

    authors: Fisher PJ,Gardner RC,Richardson TE

    更新日期:1996-11-01 00:00:00

  • Summaries of Affymetrix GeneChip probe level data.

    abstract::High density oligonucleotide array technology is widely used in many areas of biomedical research for quantitative and highly parallel measurements of gene expression. Affymetrix GeneChip arrays are the most popular. In this technology each gene is typically represented by a set of 11-20 pairs of probes. In order to o...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gng015

    authors: Irizarry RA,Bolstad BM,Collin F,Cope LM,Hobbs B,Speed TP

    更新日期:2003-02-15 00:00:00

  • DNA methylation in hereditary persistence of fetal hemoglobin (HPFH-2).

    abstract::Recent studies show that the region of DNA brought into close proximity to the fetal gamma-globin genes in deletional forms of hereditary persistence of fetal hemoglobin (HPFH) is selectively hypomethylated (and presumably active) in normal erythroid tissue. This region is normally located approximately 100 kilobases ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/15.13.5169

    authors: Poncz M,Sutton M,Delgrosso K,Schwartz E,Surrey S

    更新日期:1987-07-10 00:00:00

  • Multivariate curve resolution: a powerful tool for the analysis of conformational transitions in nucleic acids.

    abstract::A successful application is reported of the multivariate curve resolution alternating least-squares method (MCR-ALS) for the analysis of nucleic acid melting and salt-induced transitions. Under conditions where several structures co-exist in a conformational equilibrium, MCR-ALS analysis of the UV and circular dichroi...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gnf091

    authors: Jaumot J,Escaja N,Gargallo R,González C,Pedroso E,Tauler R

    更新日期:2002-09-01 00:00:00

  • DNA topology of the ordered chromatin domain 5' to the human c-myc gene.

    abstract::DNA restriction fragments located 5' to the human c-myc gene display anomalous electrophoretic mobility on polyacrylamide gels. Computer modeling of the c-myc flanking DNA suggests that the slow-moving DNA fragments spanning nucleotides -1690 to -1054 (relative to c-myc promoter P1) and -718 to -452 form large left ha...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/17.7.2819

    authors: Kumar S,Leffak M

    更新日期:1989-04-11 00:00:00

  • DOT1L promotes progenitor proliferation and primes neuronal layer identity in the developing cerebral cortex.

    abstract::Cortical development is controlled by transcriptional programs, which are orchestrated by transcription factors. Yet, stable inheritance of spatio-temporal activity of factors influencing cell fate and localization in different layers is only partly understood. Here we find that deletion of Dot1l in the murine telence...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gky953

    authors: Franz H,Villarreal A,Heidrich S,Videm P,Kilpert F,Mestres I,Calegari F,Backofen R,Manke T,Vogel T

    更新日期:2019-01-10 00:00:00

  • Systematic prediction of genes functionally associated with bacterial retrons and classification of the encoded tripartite systems.

    abstract::Bacterial retrons consist of a reverse transcriptase (RT) and a contiguous non-coding RNA (ncRNA) gene. One third of annotated retrons carry additional open reading frames (ORFs), the contribution and significance of which in retron biology remains to be determined. In this study we developed a computational pipeline ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa1149

    authors: Mestre MR,González-Delgado A,Gutiérrez-Rus LI,Martínez-Abarca F,Toro N

    更新日期:2020-12-16 00:00:00

  • Interaction of dimeric intercalating dyes with single-stranded DNA.

    abstract::The unsymmetrical cyanine dye thiazole orange homodimer (TOTO) binds to single-stranded DNA (ssDNA, M13mp18 ssDNA) to form a fluorescent complex that is stable under the standard conditions of electrophoresis. The stability of this complex is indistinguishable from that of the corresponding complex of TOTO with double...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/23.7.1215

    authors: Rye HS,Glazer AN

    更新日期:1995-04-11 00:00:00

  • Molecular footprints of human immunoglobulin gene evolution: a new sequence family.

    abstract::Analysis of the human VK (ref. 2) gene locus led to the detection of a new sequence family (L sequences). Its copy number is in the range of 10(2). The L sequences, which are about 500 bp long, are found as part of the 3' flanking regions of a clustered set of human VKI genes but they occur also separate from the gene...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/12.13.5265

    authors: Straubinger B,Pech M,Mühlebach K,Jaenichen HR,Bauer HG,Zachau HG

    更新日期:1984-07-11 00:00:00

  • A computer program to enter DNA gel reading data into a computer.

    abstract::This paper describes a simple program that uses a digitizing device to enter DNA sequences directly from autoradiographs into a computer. ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/12.1part2.499

    authors: Staden R

    更新日期:1984-01-11 00:00:00

  • Effects of hypoxanthine substitution on bleomycin-mediated DNA strand degradation in DNA-RNA hybrids.

    abstract::We have reported on the differences in site-specific cleavage between DNA and DNA-RNA hybrids by various prototypic DNA cleavers (accompanying paper). In the case of bleomycin (BLM), degradation at 5'-GC-3'sites was suppressed relative to the same sequence in double-stranded DNA, while 5'-GT-3' damage remained constan...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/25.9.1846

    authors: Bansal M,Stubbe J,Kozarich JW

    更新日期:1997-05-01 00:00:00

  • 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...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/18.24.7259

    authors: Mullineaux PM,Guerineau F,Accotto GP

    更新日期:1990-12-25 00:00:00

  • A hand-off of DNA between archaeal polymerases allows high-fidelity replication to resume at a discrete intermediate three bases past 8-oxoguanine.

    abstract::During DNA replication, the presence of 8-oxoguanine (8-oxoG) lesions in the template strand cause the high-fidelity (HiFi) DNA polymerase (Pol) to stall. An early response to 8-oxoG lesions involves 'on-the-fly' translesion synthesis (TLS), in which a specialized TLS Pol is recruited and replaces the stalled HiFi Pol...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa803

    authors: Cranford MT,Kaszubowski JD,Trakselis MA

    更新日期:2020-11-04 00:00:00

  • Comparison of loop extrusion and diffusion capture as mitotic chromosome formation pathways in fission yeast.

    abstract::Underlying higher order chromatin organization are Structural Maintenance of Chromosomes (SMC) complexes, large protein rings that entrap DNA. The molecular mechanism by which SMC complexes organize chromatin is as yet incompletely understood. Two prominent models posit that SMC complexes actively extrude DNA loops (l...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkaa1270

    authors: Gerguri T,Fu X,Kakui Y,Khatri BS,Barrington C,Bates PA,Uhlmann F

    更新日期:2021-01-12 00:00:00

  • A cDNA clone of the hnRNP C proteins and its homology with the single-stranded DNA binding protein UP2.

    abstract::A cDNA clone which expresses a protein that cross-reacts immunologically with the human C1 and C2 hnRNP core proteins has been isolated. The clone was selected by a sensitive immunochemical assay employing an avidin-biotin complex for detection, and identified as a clone for the hnRNP C proteins by a highly sensitive ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/14.10.4077

    authors: Lahiri DK,Thomas JO

    更新日期:1986-05-27 00:00:00

  • Genomics of Drug Sensitivity in Cancer (GDSC): a resource for therapeutic biomarker discovery in cancer cells.

    abstract::Alterations in cancer genomes strongly influence clinical responses to treatment and in many instances are potent biomarkers for response to drugs. The Genomics of Drug Sensitivity in Cancer (GDSC) database (www.cancerRxgene.org) is the largest public resource for information on drug sensitivity in cancer cells and mo...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gks1111

    authors: Yang W,Soares J,Greninger P,Edelman EJ,Lightfoot H,Forbes S,Bindal N,Beare D,Smith JA,Thompson IR,Ramaswamy S,Futreal PA,Haber DA,Stratton MR,Benes C,McDermott U,Garnett MJ

    更新日期:2013-01-01 00:00:00

  • Exocyclic amino groups of flanking guanines govern sequence-dependent adduct conformations and local structural distortions for minor groove-aligned benzo[a]pyrenyl-guanine lesions in a GG mutation hotspot context.

    abstract::The environmental carcinogen benzo[a]pyrene (BP) is metabolized to reactive diol epoxides that bind to cellular DNA by predominantly forming N2-guanine adducts (G*). Mutation hotspots for these adducts are frequently found in 5'- ... GG ... dinucleotide sequences, but their origins are poorly understood. Here we used ...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkm022

    authors: Rodríguez FA,Cai Y,Lin C,Tang Y,Kolbanovskiy A,Amin S,Patel DJ,Broyde S,Geacintov NE

    更新日期:2007-01-01 00:00:00

  • Annealing helicase HARP closes RPA-stabilized DNA bubbles non-processively.

    abstract::We investigate the mechanistic nature of the Snf2 family protein HARP, mutations of which are responsible for Schimke immuno-osseous dysplasia. Using a single-molecule magnetic tweezers assay, we construct RPA-stabilized DNA bubbles within torsionally constrained DNA to investigate the annealing action of HARP on a ph...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkx147

    authors: Burnham DR,Nijholt B,De Vlaminck I,Quan J,Yusufzai T,Dekker C

    更新日期:2017-05-05 00:00:00

  • RPI-Pred: predicting ncRNA-protein interaction using sequence and structural information.

    abstract::RNA-protein complexes are essential in mediating important fundamental cellular processes, such as transport and localization. In particular, ncRNA-protein interactions play an important role in post-transcriptional gene regulation like mRNA localization, mRNA stabilization, poly-adenylation, splicing and translation....

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gkv020

    authors: Suresh V,Liu L,Adjeroh D,Zhou X

    更新日期:2015-02-18 00:00:00

  • Genome maintenance in Saccharomyces cerevisiae: the role of SUMO and SUMO-targeted ubiquitin ligases.

    abstract::The genome of the cell is often exposed to DNA damaging agents and therefore requires an intricate well-regulated DNA damage response (DDR) to overcome its deleterious effects. The DDR needs proper regulation for its timely activation, repression, as well as appropriate choice of repair pathway. Studies in Saccharomyc...

    journal_title:Nucleic acids research

    pub_type: 杂志文章,评审

    doi:10.1093/nar/gkw1369

    authors: Jalal D,Chalissery J,Hassan AH

    更新日期:2017-03-17 00:00:00

  • Predominance of six different hexanucleotide recoding signals 3' of read-through stop codons.

    abstract::Redefinition of UAG, UAA and UGA to specify a standard amino acid occurs in response to recoding signals present in a minority of mRNAs. This 'read-through' is in competition with termination and is utilized for gene expression. One of the recoding signals known to stimulate read-through is a hexanucleotide sequence o...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/30.9.2011

    authors: Harrell L,Melcher U,Atkins JF

    更新日期:2002-05-01 00:00:00

  • The ATP-mediated formation of the YgjD-YeaZ-YjeE complex is required for the biosynthesis of tRNA t6A in Escherichia coli.

    abstract::The essential and universal N(6)-threonylcarbamoyladenosine (t(6)A) modification at position 37 of ANN-decoding tRNAs plays a pivotal role in translational fidelity through enhancement of the cognate codon recognition and stabilization of the codon-anticodon interaction. In Escherichia coli, the YgjD (TsaD), YeaZ (Tsa...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/gku1397

    authors: Zhang W,Collinet B,Perrochia L,Durand D,van Tilbeurgh H

    更新日期:2015-02-18 00:00:00

  • Correlation between DNase I hypersensitive sites and putative regulatory sequences in human immunoglobulin genes of the kappa light chain type.

    abstract::The human lymphoid cell lines Walker and Daudi constitute a particularly suitable system for studies on the chromatin structure of K light chain genes (see preceding paper). The rearranged and non-rearranged alleles of Walker cells were found to be about equally sensitive towards digestion with DNAase I. A DNAase I hy...

    journal_title:Nucleic acids research

    pub_type: 杂志文章

    doi:10.1093/nar/12.18.7007

    authors: Pospelov VA,Klobeck HG,Zachau HG

    更新日期:1984-09-25 00:00:00