Abstract:
:Hypermethylation is associated with the silencing of tumour susceptibility genes in several forms of cancer; however, the mechanisms responsible for this aberrant methylation are poorly understood. The prototypic DNA methyltransferase, DNMT1, has been widely assumed to be responsible for most of the methylation of the human genome, including the abnormal methylation found in cancers. To test this hypothesis, we disrupted the DNMT1 gene through homologous recombination in human colorectal carcinoma cells. Here we show that cells lacking DNMT1 exhibited markedly decreased cellular DNA methyltransferase activity, but there was only a 20% decrease in overall genomic methylation. Although juxtacentromeric satellites became significantly demethylated, most of the loci that we analysed, including the tumour suppressor gene p16INK4a, remained fully methylated and silenced. These results indicate that DNMT1 has an unsuspected degree of regional specificity in human cells and that methylating activities other than DNMT1 can maintain the methylation of most of the genome.
journal_name
Naturejournal_title
Natureauthors
Rhee I,Jair KW,Yen RW,Lengauer C,Herman JG,Kinzler KW,Vogelstein B,Baylin SB,Schuebel KEdoi
10.1038/35010000keywords:
subject
Has Abstractpub_date
2000-04-27 00:00:00pages
1003-7issue
6781eissn
0028-0836issn
1476-4687journal_volume
404pub_type
杂志文章相关文献
NATURE文献大全abstract::Light absorption by the visual pigment rhodopsin triggers, through G-protein coupling, a cascade of events in the outer segment of the rod cell of the vertebrate retina that results in membrane hyperpolarization and nerve excitation. Rhodopsin, which contains 348 amino acids, has seven helices that cross the disk memb...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/362770a0
更新日期:1993-04-22 00:00:00
abstract::The contractile proteins of adult skeletal and cardiac muscle tissue are very similar. Some of these proteins are identical in amino acid sequence or differ only slightly. Various structural studies have shown that the heavy and light chains of myosin are also homologous in skeletal and cardiac muscles. In developing ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/286731a0
更新日期:1980-08-14 00:00:00
abstract::Double-stranded RNAs (dsRNAs) induce post-transcriptional gene silencing in several species of animal and plant. In plants, dsRNAs targeted to CpG islands within a promoter can also induce RNA-directed DNA methylation; however, it remains unclear whether gene silencing mediated by DNA methylation can be induced by dsR...
journal_title:Nature
pub_type: 杂志文章,收录出版
doi:10.1038/nature02889
更新日期:2004-09-09 00:00:00
abstract::The National Institutes of Health's Recombinant DNA Advisory Committee (RAC) has approved a commercial proposal by Advanced Genetic Sciences Inc. to field-test recombinant ice-nucleating bacteria. Its decision came two weeks after a federal judge halted a similar trial by researchers from the University of California...
journal_title:Nature
pub_type: 新闻
doi:10.1038/309483a0
更新日期:1984-06-07 00:00:00
abstract::Is the big-bang hot, warm or cold? And are galactic masses determined by the interplay of gravitational and strong interactions in the very early universe? ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/228258a0
更新日期:1970-10-17 00:00:00
abstract::The RIG-like helicase (RLH) family of intracellular receptors detect viral nucleic acid and signal through the mitochondrial antiviral signalling adaptor MAVS (also known as Cardif, VISA and IPS-1) during a viral infection. MAVS activation leads to the rapid production of antiviral cytokines, including type 1 interfer...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature06501
更新日期:2008-01-31 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 评论,新闻
doi:10.1038/d41586-019-00393-6
更新日期:2019-02-01 00:00:00
abstract::The abundant nuclear enzyme poly(ADP-ribose) polymerase catalyses the synthesis of poly(ADP-ribose) from nicotinamide adenine dinucleotide (NAD+). This protein has an N-terminal DNA-binding domain containing two zinc-fingers, which is linked to the C-terminal NAD(+)-binding domain by a short region containing several ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/356356a0
更新日期:1992-03-26 00:00:00
abstract::Activated T lymphocytes differentiate into effector cells tailored to meet disparate challenges to host integrity. For example, type 1 and type 2 helper (T(H)1 and T(H)2) cells secrete cytokines that enhance cell-mediated and humoral immunity, respectively. The chemokine monocyte chemoattractant protein-1 (MCP-1) can ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35006097
更新日期:2000-03-23 00:00:00
abstract::In this Letter, owing to a copying error in Illustrator, the two centre panels in Extended Data Fig. 7a were identical. This error has been corrected online. The old, incorrect Extended Data Fig. 7 is shown in the Supplementary Information to this Amendment for transparency. Some typos ('occurence') in Figs. 1, 2 and ...
journal_title:Nature
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41586-018-0231-y
更新日期:2018-07-01 00:00:00
abstract::The partial amino-acid sequence of purified human transforming growth factor-beta (TGF-beta) was used to identify a series of cDNA clones encoding the protein. The cDNA sequence indicates that the 112-amino acid monomeric form of the natural TGF-beta homodimer is derived proteolytically from a much longer precursor po...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/316701a0
更新日期:1985-08-22 00:00:00
abstract::Calcium (Ca(2+))-activated chloride channels are fundamental mediators in numerous physiological processes including transepithelial secretion, cardiac and neuronal excitation, sensory transduction, smooth muscle contraction and fertilization. Despite their physiological importance, their molecular identity has remain...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature07313
更新日期:2008-10-30 00:00:00
abstract::The molecular and cellular basis of T-lymphocyte activation remains a central question in immunology. The growth of already proliferating T cells is known to depend on T-cell growth factor (TCGF), a physiological mitogen. Noncycling T lymphocytes, however, are not sensitive to TCGF. They require a short contact with m...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/283664a0
更新日期:1980-02-14 00:00:00
abstract::It has been shown that Neanderthals contributed genetically to modern humans outside Africa 47,000-65,000 years ago. Here we analyse the genomes of a Neanderthal and a Denisovan from the Altai Mountains in Siberia together with the sequences of chromosome 21 of two Neanderthals from Spain and Croatia. We find that a p...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature16544
更新日期:2016-02-25 00:00:00
abstract::In the chick embryo, left-right asymmetric patterns of gene expression in the lateral plate mesoderm are initiated by signals located in and around Hensen's node. Here we show that Caronte (Car), a secreted protein encoded by a member of the Cerberus/Dan gene family, mediates the Sonic hedgehog (Shh)-dependent inducti...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/45738
更新日期:1999-09-16 00:00:00
abstract::Crossover recombination events between homologous chromosomes are required to form chiasmata, temporary connections between homologues that ensure their proper segregation at meiosis I. Despite this requirement for crossovers and an excess of the double-strand DNA breaks that are the initiating events for meiotic reco...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12577
更新日期:2013-10-31 00:00:00
abstract::We are facing a global metabolic health crisis provoked by an obesity epidemic. Here we report the human gut microbial composition in a population sample of 123 non-obese and 169 obese Danish individuals. We find two groups of individuals that differ by the number of gut microbial genes and thus gut bacterial richness...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12506
更新日期:2013-08-29 00:00:00
abstract::Quantum degenerate Fermi gases provide a remarkable opportunity to study strongly interacting fermions. In contrast to other Fermi systems, such as superconductors, neutron stars or the quark-gluon plasma of the early Universe, these gases have low densities and their interactions can be precisely controlled over an e...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature03858
更新日期:2005-06-23 00:00:00
abstract::The first event in the initiation of an immune response is the capture and presentation of antigen to T cells. Such presentation involves two distinct steps: (1) display of the antigen, which requires uptake, processing and re-expression of the antigen in association with MHC molecules on the presenting cell surface; ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/334253a0
更新日期:1988-07-21 00:00:00
abstract::Calnexin, an endoplasmic reticulum transmembrane protein, represents a new type of molecular chaperone that selectively associates in a transient fashion with newly synthesized monomeric glycoproteins in HepG2 cells. Calnexin only recognizes glycoproteins when they are incompletely folded. Dissociation of glycoprotein...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/364771a0
更新日期:1993-08-26 00:00:00
abstract::Ten eleven translocation (TET) enzymes, including TET1, TET2 and TET3, convert 5-methylcytosine to 5-hydroxymethylcytosine and regulate gene transcription. However, the molecular mechanism by which TET family enzymes regulate gene transcription remains elusive. Using protein affinity purification, here we search for f...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature11742
更新日期:2013-01-24 00:00:00
abstract::Human T-cell leukaemia virus (HTLV), first isolated in the United States from a patient with cutaneous T-cell lymphoma, is a unique horizontally transmitted retrovirus which is highly associated with certain adult T-cell malignancies. Also, HTLV can be transmitted in vitro to cord blood T-lymphocytes. In the accompany...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/305060a0
更新日期:1983-09-01 00:00:00
abstract::The discovery of intervening sequences (introns) in DNA led Gilbert and Tonegawa to suggest that a new protein could have been produced by bringing together certain segments of pre-existing ones. However, Blake argued that if DNA was so organized that coding sequences (exons) correspond to structural as well as functi...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/291090a0
更新日期:1981-05-07 00:00:00
abstract::During the fission yeast cell cycle, the rate of polyadenylated messenger RNA synthesis doubles when the cell reaches a critical size. This size-related control maintains average mRNA content in balance with total cell mass during exponential growth, even in cells growing at different absolute growth rates per cell. ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/271726a0
更新日期:1978-02-23 00:00:00
abstract::The dispersal of early humans from Africa by 1.75 Myr ago led to a marked expansion of their range, from the island of Flores in the east to the Iberian peninsula in the west. This range encompassed tropical forest, savannah and Mediterranean habitats, but has hitherto not been demonstrated beyond 45 degrees N. Until ...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/nature09117
更新日期:2010-07-08 00:00:00
abstract::Sex differences in behaviour extend to cognitive-like processes such as learning, but the underlying dimorphisms in neural circuit development and organization that generate these behavioural differences are largely unknown. Here we define at the single-cell level-from development, through neural circuit connectivity,...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature15700
更新日期:2015-10-15 00:00:00
abstract::Conrad et al. have generated human adult germline stem cells (haGSCs) from human testicular tissue, which they claim have similar pluripotent properties to human embryonic stem cells (hESCs). Here we investigate the pluripotency of haGSCs by using global gene-expression analysis based on their gene array data and comp...
journal_title:Nature
pub_type: 评论,杂志文章
doi:10.1038/nature09089
更新日期:2010-06-24 00:00:00
abstract::Pluto's tenuous nitrogen atmosphere was first detected by the imprint left on the light curve of a star that was occulted by the planet in 1985 (ref. 1), and studied more extensively during a second occultation event in 1988 (refs 2-6). These events are, however, quite rare and Pluto's atmosphere remains poorly unders...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01766
更新日期:2003-07-10 00:00:00
abstract::Double-walled carbon nanotubes are needed in a pure, highly crystalline form before features such as their electronic properties, thermal transport and mechanical behaviour can be investigated. Here we fabricate a paper-like material that consists of hexagonally packed bundles of clean, coaxial carbon nanotubes whose ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/433476a
更新日期:2005-02-03 00:00:00
abstract::CYCLINS are proteins synthesized during each cell cycle and abruptly destroyed in each mitosis. Cyclins have been implicated in the induction of mitosis and are associated with the serine-threonine protein kinase p34cdc2 as components of mitosis promoting factor (MPF). On the basis of conserved sequence motifs cyclins...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/346760a0
更新日期:1990-08-23 00:00:00