当前位置： SCI文献检索 > NATURE期刊下所有文献 > Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA.

Epigenetic silencing of tumour suppressor gene p15 by its antisense RNA.

Abstract：

:Tumour suppressor genes (TSGs) inhibiting normal cellular growth are frequently silenced epigenetically in cancer. DNA methylation is commonly associated with TSG silencing, yet mutations in the DNA methylation initiation and recognition machinery in carcinogenesis are unknown. An intriguing possible mechanism for gene regulation involves widespread non-coding RNAs such as microRNA, Piwi-interacting RNA and antisense RNAs. Widespread sense-antisense transcripts have been systematically identified in mammalian cells, and global transcriptome analysis shows that up to 70% of transcripts have antisense partners and that perturbation of antisense RNA can alter the expression of the sense gene. For example, it has been shown that an antisense transcript not naturally occurring but induced by genetic mutation leads to gene silencing and DNA methylation, causing thalassaemia in a patient. Here we show that many TSGs have nearby antisense RNAs, and we focus on the role of one RNA in silencing p15, a cyclin-dependent kinase inhibitor implicated in leukaemia. We found an inverse relation between p15 antisense (p15AS) and p15 sense expression in leukaemia. A p15AS expression construct induced p15 silencing in cis and in trans through heterochromatin formation but not DNA methylation; the silencing persisted after p15AS was turned off, although methylation and heterochromatin inhibitors reversed this process. The p15AS-induced silencing was Dicer-independent. Expression of exogenous p15AS in mouse embryonic stem cells caused p15 silencing and increased growth, through heterochromatin formation, as well as DNA methylation after differentiation of the embryonic stem cells. Thus, natural antisense RNA may be a trigger for heterochromatin formation and DNA methylation in TSG silencing in tumorigenesis.

journal_name

Nature

journal_title

Nature

authors

Yu W,Gius D,Onyango P,Muldoon-Jacobs K,Karp J,Feinberg AP,Cui H

doi

10.1038/nature06468

subject

Has Abstract

pub_date

2008-01-10 00:00:00

pages

202-6

issue

7175

eissn

0028-0836

issn

1476-4687

pii

nature06468

journal_volume

451

pub_type

杂志文章

相关文献

NATURE文献大全
  • The t(8; 14) chromosomal translocation occurring in B-cell malignancies results from mistakes in V-D-J joining.

    abstract：:The reciprocal chromosome translocation, t(8;14), involving the heavy chain locus on chromosome 14 and the c-myc oncogene on chromosome 8 is a characteristic of the B-cell malignancies Burkitt's lymphoma and acute lymphoblastic leukaemia (ALL). We have cloned and sequenced the t(8; 14) breakpoints of an African Burkit...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/324158a0

    authors： Haluska FG,Finver S,Tsujimoto Y,Croce CM

    更新日期：1986-11-13 00:00:00

  • Deep-sea ecology. Developmental arrest in vent worm embryos.

    abstract：:Temperature is a key factor in controlling the distribution of marine organisms and is particularly important at hydrothermal vents, where steep thermal gradients are present over a scale of centimetres. The thermophilic worm Alvinella pompejana, which is found at the vents of the East Pacific Rise (2,500-m depth), ha...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/35099674

    authors： Pradillon F,Shillito B,Young CM,Gaill F

    更新日期：2001-10-18 00:00:00

  • Direct measurement of proton transfer rates to a group controlling the dihydropyridine-sensitive Ca2+ channel.

    abstract：:Protons participate in most biologically important reactions, as substrates, products, cofactors and modulators, and proton transport is an essential step in energy transduction. The dynamics of protonation reactions have been studied extensively in solution and in model systems involving lipid-water interfaces, but h...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/329243a0

    authors： Prod'hom B,Pietrobon D,Hess P

    更新日期：1987-09-17 00:00:00

  • Dependence of Z-DNA antibody binding to polytene chromosomes on acid fixation and DNA torsional strain.

    abstract：:There is considerable interest in the existence and significance of alternative conformations of DNA to the right-handed B-form described originally by Watson and Crick. The indirect immunofluorescence observations of Nordheim et al., Arndt-Jovin et al. and Lemeunier et al. that antibodies against left-handed Z-DNA bi...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/305338a0

    authors： Hill RJ,Stollar BD

    更新日期：1983-09-22 00:00:00

  • Na channels in skeletal muscle concentrated near the neuromuscular junction.

    abstract：:Neuronal function depends crucially on the spatial segregation of specific membrane proteins, particularly the segregation associated with sites of synaptic contact. Understanding the factors governing this localization of proteins is a major goal of cellular neurobiology. A conspicuous example of synaptic specializat...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/313588a0

    authors： Beam KG,Caldwell JH,Campbell DT

    更新日期：1985-02-14 00:00:00

  • Combined effects of angiostatin and ionizing radiation in antitumour therapy.

    abstract：:Angiogenesis, the formation of new capillaries from pre-existing vessels, is essential for tumour progression. Angiostatin, a proteolytic fragment of plasminogen that was first isolated from the serum and urine of tumour-bearing mice, inhibits angiogenesis and thereby growth of primary and metastatic tumours. Radiothe...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/28412

    authors： Mauceri HJ,Hanna NN,Beckett MA,Gorski DH,Staba MJ,Stellato KA,Bigelow K,Heimann R,Gately S,Dhanabal M,Soff GA,Sukhatme VP,Kufe DW,Weichselbaum RR

    更新日期：1998-07-16 00:00:00

  • Mutations in the hepatocyte nuclear factor-1alpha gene in maturity-onset diabetes of the young (MODY3)

    abstract：:The disease non-insulin-dependent (type 2) diabetes mellitus (NIDDM) is characterized by abnormally high blood glucose resulting from a relative deficiency of insulin. It affects about 2% of the world's population and treatment of diabetes and its complications are an increasing health-care burden. Genetic factors are...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/384455a0

    authors： Yamagata K,Oda N,Kaisaki PJ,Menzel S,Furuta H,Vaxillaire M,Southam L,Cox RD,Lathrop GM,Boriraj VV,Chen X,Cox NJ,Oda Y,Yano H,Le Beau MM,Yamada S,Nishigori H,Takeda J,Fajans SS,Hattersley AT,Iwasaki N,Hansen T,

    更新日期：1996-12-05 00:00:00

  • A high-resolution map of the three-dimensional chromatin interactome in human cells.

    abstract：:A large number of cis-regulatory sequences have been annotated in the human genome, but defining their target genes remains a challenge. One strategy is to identify the long-range looping interactions at these elements with the use of chromosome conformation capture (3C)-based techniques. However, previous studies lac...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature12644

    authors： Jin F,Li Y,Dixon JR,Selvaraj S,Ye Z,Lee AY,Yen CA,Schmitt AD,Espinoza CA,Ren B

    更新日期：2013-11-14 00:00:00

  • Topological domains in mammalian genomes identified by analysis of chromatin interactions.

    abstract：:The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct chromosome territories, and numerous models have been proposed...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature11082

    authors： Dixon JR,Selvaraj S,Yue F,Kim A,Li Y,Shen Y,Hu M,Liu JS,Ren B

    更新日期：2012-04-11 00:00:00

  • Carbon isotope composition of individual amino acids in the Murchison meteorite.

    abstract：:A significant portion of prebiotic organic matter on the early Earth may have been introduced by carbonaceous asteroids and comets. The distribution and stable-isotope composition of individual organic compounds in carbonaceous meteorites, which are thought to be derived from asteroidal parent bodies, may therefore pr...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/348047a0

    authors： Engel MH,Macko SA,Silfer JA

    更新日期：1990-11-01 00:00:00

  • Greater contribution to blood lead from water than from air.

    abstract：:Concern about the levels of lead in blood is widespread. There is uncertainty, however, about the relative importance of the various environmental sources. Lead in petrol is widely assumed to be one of the most important sources and air and dust have been identified as the main routes to man. Water is regarded as an i...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/310138a0

    authors： Elwood PC,Gallacher JE,Phillips KM,Davies BE,Toothill C

    更新日期：1984-07-12 00:00:00

  • The reaction mechanism of the internal thioester in the human complement component C4.

    abstract：:A key step in the elimination of pathogens from the body is the covalent binding of complement proteins C3 and C4 to their surfaces. Proteolytic activation of these proteins results in a conformational change, and an internal thioester is exposed which reacts with amino or hydroxyl groups on the target surface to form...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/379177a0

    authors： Dodds AW,Ren XD,Willis AC,Law SK

    更新日期：1996-01-11 00:00:00

  • Reversible events in the transduction process of photoreceptors.

    abstract：:In photoreceptors, a latency of many milliseconds elapses between the absorption of a light quantum and the occurrence of the late receptor potential, even for strong light stimuli. Surprisingly, this is much longer than the time necessary for conductance changes such as occur in membranes of neurones or muscles, medi...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/283859a0

    authors： Hamdorf K,Kirschfeld K

    更新日期：1980-02-28 00:00:00

  • A deficiency of the homeotic complex of the beetle Tribolium.

    abstract：:In Drosophila, the establishment of regional commitments along most of the anterior/posterior axis of the developing embryo depends on two clusters of homeotic genes: the Antennapedia complex (ANT-C) and the bithorax complex (BX-C). The red flour beetle has a single complex (HOM-C) representing the homologues of the...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/350072a0

    authors： Stuart JJ,Brown SJ,Beeman RW,Denell RE

    更新日期：1991-03-07 00:00:00

  • Near-atomic-resolution cryo-EM analysis of the Salmonella T3S injectisome basal body.

    abstract：:The type III secretion (T3S) injectisome is a specialized protein nanomachine that is critical for the pathogenicity of many Gram-negative bacteria, including purveyors of plague, typhoid fever, whooping cough, sexually transmitted infections and major nosocomial infections. This syringe-shaped 3.5-MDa macromolecular ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature20576

    authors： Worrall LJ,Hong C,Vuckovic M,Deng W,Bergeron JRC,Majewski DD,Huang RK,Spreter T,Finlay BB,Yu Z,Strynadka NCJ

    更新日期：2016-12-22 00:00:00

  • Poly(dA).poly(dT) is a B-type double helix with a distinctively narrow minor groove.

    abstract：:The structure of poly(dA).poly(dT) currently arouses great interest, mainly because dAn.dTn stretches are associated with considerable DNA bending. Until recently the heteronomous DNA described by Arnott et al., with the poly(dA) and poly(dT) chains in A and B conformations respectively, was the only detailed model of...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/325821a0

    authors： Alexeev DG,Lipanov AA,Skuratovskii IYa

    更新日期：1987-02-26 00:00:00

  • Structure of the Fc fragment of human IgE bound to its high-affinity receptor Fc epsilonRI alpha.

    abstract：:The initiation of immunoglobulin-E (IgE)-mediated allergic responses requires the binding of IgE antibody to its high-affinity receptor, Fc epsilonRI. Crosslinking of Fc epsilonRI initiates an intracellular signal transduction cascade that triggers the release of mediators of the allergic response. The interaction of ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/35018500

    authors： Garman SC,Wurzburg BA,Tarchevskaya SS,Kinet JP,Jardetzky TS

    更新日期：2000-07-20 00:00:00

  • Defensin-like polypeptide LUREs are pollen tube attractants secreted from synergid cells.

    abstract：:For more than 140 years, pollen tube guidance in flowering plants has been thought to be mediated by chemoattractants derived from target ovules. However, there has been no convincing evidence of any particular molecule being the true attractant that actually controls the navigation of pollen tubes towards ovules. Eme...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature07882

    authors： Okuda S,Tsutsui H,Shiina K,Sprunck S,Takeuchi H,Yui R,Kasahara RD,Hamamura Y,Mizukami A,Susaki D,Kawano N,Sakakibara T,Namiki S,Itoh K,Otsuka K,Matsuzaki M,Nozaki H,Kuroiwa T,Nakano A,Kanaoka MM,Dresselhaus T,Sa

    更新日期：2009-03-19 00:00:00

  • Genome sequencing in microfabricated high-density picolitre reactors.

    abstract：:The proliferation of large-scale DNA-sequencing projects in recent years has driven a search for alternative methods to reduce time and cost. Here we describe a scalable, highly parallel sequencing system with raw throughput significantly greater than that of state-of-the-art capillary electrophoresis instruments. The...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature03959

    authors： Margulies M,Egholm M,Altman WE,Attiya S,Bader JS,Bemben LA,Berka J,Braverman MS,Chen YJ,Chen Z,Dewell SB,Du L,Fierro JM,Gomes XV,Godwin BC,He W,Helgesen S,Ho CH,Irzyk GP,Jando SC,Alenquer ML,Jarvie TP,Jirage K

    更新日期：2005-09-15 00:00:00

  • Evasion of the p53 tumour surveillance network by tumour-derived MYC mutants.

    abstract：:The c-Myc oncoprotein promotes proliferation and apoptosis, such that mutations that disable apoptotic programmes often cooperate with MYC during tumorigenesis. Here we report that two common mutant MYC alleles derived from human Burkitt's lymphoma uncouple proliferation from apoptosis and, as a result, are more effec...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature03845

    authors： Hemann MT,Bric A,Teruya-Feldstein J,Herbst A,Nilsson JA,Cordon-Cardo C,Cleveland JL,Tansey WP,Lowe SW

    更新日期：2005-08-11 00:00:00

  • Monoclonal anti-Fc receptor IgG blocks antibody enhancement of viral replication in macrophages.

    abstract：:Flaviviruses, when complexed with antibody at subneutralizing concentrations, show enhanced replication in human and simian peripheral blood leukocytes (ref. 1, and J.S.M.P. and J.S.P., unpublished observations) and in P388 D1 and other macrophage cell lines. A comparable phenomenon has been demonstrated with alphavir...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/289189a0

    authors： Peiris JS,Gordon S,Unkeless JC,Porterfield JS

    更新日期：1981-01-15 00:00:00

  • An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer.

    abstract：:The clinical development of an inhibitor of cellular proteasome function suggests that compounds targeting other components of the ubiquitin-proteasome system might prove useful for the treatment of human malignancies. NEDD8-activating enzyme (NAE) is an essential component of the NEDD8 conjugation pathway that contro...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature07884

    authors： Soucy TA,Smith PG,Milhollen MA,Berger AJ,Gavin JM,Adhikari S,Brownell JE,Burke KE,Cardin DP,Critchley S,Cullis CA,Doucette A,Garnsey JJ,Gaulin JL,Gershman RE,Lublinsky AR,McDonald A,Mizutani H,Narayanan U,Olhava EJ

    更新日期：2009-04-09 00:00:00

  • A kiloparsec-scale internal shock collision in the jet of a nearby radio galaxy.

    abstract：:Jets of highly energized plasma with relativistic velocities are associated with black holes ranging in mass from a few times that of the Sun to the billion-solar-mass black holes at the centres of galaxies. A popular but unconfirmed hypothesis to explain how the plasma is energized is the 'internal shock model', in w...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature14481

    authors： Meyer ET,Georganopoulos M,Sparks WB,Perlman E,van der Marel RP,Anderson J,Sohn ST,Biretta J,Norman C,Chiaberge M

    更新日期：2015-05-28 00:00:00

  • Genetic evidence for Near-Eastern origins of European cattle.

    abstract：:The limited ranges of the wild progenitors of many of the primary European domestic species point to their origins further east in Anatolia or the fertile crescent. The wild ox (Bos primigenius), however, ranged widely and it is unknown whether it was domesticated within Europe as one feature of a local contribution t...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/35074088

    authors： Troy CS,MacHugh DE,Bailey JF,Magee DA,Loftus RT,Cunningham P,Chamberlain AT,Sykes BC,Bradley DG

    更新日期：2001-04-26 00:00:00

  • Agonist/endogenous peptide-MHC heterodimers drive T cell activation and sensitivity.

    abstract：:Alphabeta T lymphocytes are able to detect even a single peptide-major histocompatibility complex (MHC) on the surface of an antigen-presenting cell. This is despite clear evidence, at least with CD4+ T cells, that monomeric ligands are not stimulatory. In an effort to understand how this remarkable sensitivity is ach...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature03391

    authors： Krogsgaard M,Li QJ,Sumen C,Huppa JB,Huse M,Davis MM

    更新日期：2005-03-10 00:00:00

  • S-nitrosylation of NADPH oxidase regulates cell death in plant immunity.

    abstract：:Changes in redox status are a conspicuous feature of immune responses in a variety of eukaryotes, but the associated signalling mechanisms are not well understood. In plants, attempted microbial infection triggers the rapid synthesis of nitric oxide and a parallel accumulation of reactive oxygen intermediates, the lat...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/nature10427

    authors： Yun BW,Feechan A,Yin M,Saidi NB,Le Bihan T,Yu M,Moore JW,Kang JG,Kwon E,Spoel SH,Pallas JA,Loake GJ

    更新日期：2011-10-13 00:00:00

  • New approaches for brain repair-from rescue to reprogramming.

    abstract：:The ability to repair or promote regeneration within the adult human brain has been envisioned for decades. Until recently, such efforts mainly involved delivery of growth factors and cell transplants designed to rescue or replace a specific population of neurons, and the results have largely been disappointing. New a...

    journal_title：Nature

    pub_type： 杂志文章,评审

    doi：10.1038/s41586-018-0087-1

    authors： Barker RA,Götz M,Parmar M

    更新日期：2018-05-01 00:00:00

  • Rocket UV flash spectra from the solar eclipse of March 7, 1970.

    abstract：:Flash spectra of the total solar eclipse throughout all its phases have been obtained in the extreme ultraviolet for the first time. ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/226249a0

    authors： Speer RJ,Garton WR,Morgan JF,Nicholls RW,Goldberg L,Parkinson WH,Reeves EM,Jones TJ,Paxton HJ,Shenton DB,Wilson R

    更新日期：1970-04-18 00:00:00

  • Construction, expression and recognition of an H-2 molecule lacking its carboxyl terminus.

    abstract：:A mouse major histocompatibility antigen (H-2) gene, encoding a novel H-2Ld molecule lacking its intracytoplasmic domain, has been constructed and introduced into mouse L-cells. The novel H-2 molecule is found on the surface of the transfected cells at the same level as L-cells transfected with the native H-2Ld gene. ...

    journal_title：Nature

    pub_type： 杂志文章

    doi：10.1038/307432a0

    authors： Murre C,Reiss CS,Bernabeu C,Chen LB,Burakoff SJ,Seidman JG

    更新日期：1984-02-02 00:00:00

  • TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity.

    abstract：:Retinoic-acid-inducible gene-I (RIG-I; also called DDX58) is a cytosolic viral RNA receptor that interacts with MAVS (also called VISA, IPS-1 or Cardif) to induce type I interferon-mediated host protective innate immunity against viral infection. Furthermore, members of the tripartite motif (TRIM) protein family, whic...

    journal_title：Nature

    pub_type： 信件

    doi：10.1038/nature05732

    authors： Gack MU,Shin YC,Joo CH,Urano T,Liang C,Sun L,Takeuchi O,Akira S,Chen Z,Inoue S,Jung JU

    更新日期：2007-04-19 00:00:00