Abstract:
:Many genes associated with CpG islands undergo de novo methylation in cancer. Studies have suggested that the pattern of this modification may be partially determined by an instructive mechanism that recognizes specifically marked regions of the genome. Using chromatin immunoprecipitation analysis, here we show that genes methylated in cancer cells are specifically packaged with nucleosomes containing histone H3 trimethylated on Lys27. This chromatin mark is established on these unmethylated CpG island genes early in development and then maintained in differentiated cell types by the presence of an EZH2-containing Polycomb complex. In cancer cells, as opposed to normal cells, the presence of this complex brings about the recruitment of DNA methyl transferases, leading to de novo methylation. These results suggest that tumor-specific targeting of de novo methylation is pre-programmed by an established epigenetic system that normally has a role in marking embryonic genes for repression.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Schlesinger Y,Straussman R,Keshet I,Farkash S,Hecht M,Zimmerman J,Eden E,Yakhini Z,Ben-Shushan E,Reubinoff BE,Bergman Y,Simon I,Cedar Hdoi
10.1038/ng1950subject
Has Abstractpub_date
2007-02-01 00:00:00pages
232-6issue
2eissn
1061-4036issn
1546-1718pii
ng1950journal_volume
39pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract::Genetic linkage studies with chromosome 21 DNA markers and mutation analysis of the beta-amyloid protein precursor gene located in 21q21.3 have indicated that early-onset Alzheimer's disease (EOAD) is a heterogeneous disorder for which at least one other chromosomal locus exists. We examined two extended histopatholog...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1292-335
更新日期:1992-12-01 00:00:00
abstract::Human cyclic haematopoiesis (cyclic neutropenia, MIM 162800) is an autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk fo...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/70544
更新日期:1999-12-01 00:00:00
abstract::Recent agreement on stable reference sequences for reporting human genetic variants now allows us to mandate the use of the allele naming conventions developed by the Human Genome Variation Society. ...
journal_title:Nature genetics
pub_type: 社论
doi:10.1038/ng0510-363
更新日期:2010-05-01 00:00:00
abstract::Leber congenital amaurosis (LCA) is a blinding retinal disease that presents within the first year after birth. Using exome sequencing, we identified mutations in the nicotinamide adenine dinucleotide (NAD) synthase gene NMNAT1 encoding nicotinamide mononucleotide adenylyltransferase 1 in eight families with LCA, incl...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.2356
更新日期:2012-09-01 00:00:00
abstract::Diffuse large B-cell lymphoma (DLBCL) is the most common form of human lymphoma. Although a number of structural alterations have been associated with the pathogenesis of this malignancy, the full spectrum of genetic lesions that are present in the DLBCL genome, and therefore the identity of dysregulated cellular path...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.892
更新日期:2011-07-31 00:00:00
abstract::Little is known about the genetic regulation of medulloblastoma dissemination, but metastatic medulloblastoma is highly associated with poor outcome. We obtained expression profiles of 23 primary medulloblastomas clinically designated as either metastatic (M+) or non-metastatic (M0) and identified 85 genes whose expre...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng731
更新日期:2001-10-01 00:00:00
abstract::A new study has identified rare de novo mutations in SHANK2 in individuals with autism and/or mental retardation. SHANK2 encodes a scaffolding protein present in excitatory synapses. This finding sheds some light on the pathophysiology of social and cognitive disability. ...
journal_title:Nature genetics
pub_type: 评论,新闻
doi:10.1038/ng0610-478
更新日期:2010-06-01 00:00:00
abstract::Genome-wide association studies have identified common variants that only partially explain the genetic risk for type 2 diabetes (T2D). Using genome-wide association data from 1,376 French individuals, we identified 16,360 SNPs nominally associated with T2D and studied these SNPs in an independent sample of 4,977 Fren...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.443
更新日期:2009-10-01 00:00:00
abstract::The rate and pattern of sequence substitutions in the mitochondrial DNA (mtDNA) control region (CR) is of central importance to studies of human evolution and to forensic identity testing. Here, we report a direct measurement of the intergenerational substitution rate in the human CR. We compared DNA sequences of two ...
journal_title:Nature genetics
pub_type: 杂志文章,多中心研究
doi:10.1038/ng0497-363
更新日期:1997-04-01 00:00:00
abstract::The role of human chromosome 2 in type 1 diabetes was evaluated by analysing linkage and linkage disequilibrium at 21 microsatellite marker loci, using 348 affected sibpair families and 107 simplex families. The microsatellite D2S152 was linked to, and associated with, disease in families from three different populati...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0195-80
更新日期:1995-01-01 00:00:00
abstract::Gene therapy strategies designed to combat haemophilia B, caused by defects in clotting factor IX, have so far concentrated on ex vivo approaches. We have now evaluated adenoviral vector-mediated expression of human factor IX in vivo. Injection of the vector Av1H9B, which encodes human factor IX cDNA, into the tail ve...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1293-397
更新日期:1993-12-01 00:00:00
abstract::The cardiac homeobox protein Nkx2-5 is essential in cardiac development, and mutations in Csx (which encodes Nkx2-5) cause various congenital heart diseases. Using the yeast two-hybrid system with Nkx2-5 as the 'bait', we isolated the T-box-containing transcription factor Tbx5; mutations in TBX5 cause heart and limb m...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/90123
更新日期:2001-07-01 00:00:00
abstract::Intestinal microbiota is known to be important in health and disease. Its composition is influenced by both environmental and host factors. Few large-scale studies have evaluated the association between host genetic variation and the composition of microbiota. We recruited a cohort of 1,561 healthy individuals, of who...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3693
更新日期:2016-11-01 00:00:00
abstract::Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.274
更新日期:2009-01-01 00:00:00
abstract::Tumor mutational burden correlates with response to immune checkpoint blockade in multiple solid tumors, although in microsatellite-stable tumors this association is of uncertain clinical utility. Here we uniformly analyzed whole-exome sequencing (WES) of 249 tumors and matched normal tissue from patients with clinica...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/s41588-018-0200-2
更新日期:2018-09-01 00:00:00
abstract::Immunotherapy for metastatic colorectal cancer is effective only for mismatch repair-deficient tumors with high microsatellite instability that demonstrate immune infiltration, suggesting that tumor cells can determine their immune microenvironment. To understand this cross-talk, we analyzed the transcriptome of 91,10...
journal_title:Nature genetics
pub_type: 杂志文章,多中心研究
doi:10.1038/s41588-020-0636-z
更新日期:2020-06-01 00:00:00
abstract::The amnionless gene, Amn, on mouse chromosome 12 encodes a type I transmembrane protein that is expressed in the extraembryonic visceral layer during gastrulation. Mice homozygous with respect to the amn mutation generated by a transgene insertion have no amnion. The embryos are severely compromised, surviving to the ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1098
更新日期:2003-03-01 00:00:00
abstract::Congenic breeding strategies are becoming increasingly important as a greater number of complex trait linkages are identified. Traditionally, the development of a congenic strain has been a time-consuming endeavour, requiring ten generations of backcrosses. The recent advent of a dense molecular genetic map of the mou...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1197-280
更新日期:1997-11-01 00:00:00
abstract::The Escherichia coli gene recQ was identified as a RecF recombination pathway gene. The gene SGS1, encoding the only RecQ-like DNA helicase in Saccharomyces cerevisiae, was identified by mutations that suppress the top3 slow-growth phenotype. Relatively little is known about the function of Sgs1p because single mutati...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/83673
更新日期:2001-01-01 00:00:00
abstract::The Charcot-Marie Tooth disease type 1A (CMT1A) duplication and hereditary neuropathy with liability to pressure palsies (HNPP) deletion are reciprocal products of an unequal crossing-over event between misaligned flanking CMT1A-REP repeats. The molecular aetiology of this apparently homologous recombination event was...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0396-288
更新日期:1996-03-01 00:00:00
abstract::The development of a quantitative understanding of viral evolution and the fitness landscape in HIV-1 drug resistance is a formidable challenge given the large number of available drugs and drug resistance mutations. We analyzed a dataset measuring the in vitro fitness of 70,081 virus samples isolated from HIV-1 subty...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.795
更新日期:2011-05-01 00:00:00
abstract::Micro RNAs are a large family of noncoding RNAs of 21-22 nucleotides whose functions are generally unknown. Here a large subset of Drosophila micro RNAs is shown to be perfectly complementary to several classes of sequence motif previously demonstrated to mediate negative post-transcriptional regulation. These finding...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng865
更新日期:2002-04-01 00:00:00
abstract::The vast majority of patients with fragile X syndrome show a folate-sensitive fragile site at Xq27.3 (FRAXA) at the cytogenetic level, and both amplification of the (CGG)n repeat and hypermethylation of the CpG island in the 5' fragile X gene (FMR-1) at the molecular level. We have studied the FMR-1 gene of a patient ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng0193-31
更新日期:1993-01-01 00:00:00
abstract::Plasma iron circulates bound to transferrin (Trf), which solubilizes the ferric ion and attenuates its reactivity. Diferric Trf interacts with cell-surface Trf receptor (Trfr) to undergo receptor-mediated endocytosis into specialized endosomes. Endosomal acidification leads to iron release, and iron is transported out...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/7727
更新日期:1999-04-01 00:00:00
abstract::Replication protein A (RPA) is a highly conserved single-stranded DNA-binding protein involved in DNA replication, recombination and repair. We show here that RPA is present at the telomeres of the budding yeast Saccharomyces cerevisiae, with a maximal association in S phase. A truncation of the N-terminal region of R...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1284
更新日期:2004-01-01 00:00:00
abstract::We identified homozygous truncating mutations in HOXA1 in three genetically isolated human populations. The resulting phenotype includes horizontal gaze abnormalities, deafness, facial weakness, hypoventilation, vascular malformations of the internal carotid arteries and cardiac outflow tract, mental retardation and a...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1636
更新日期:2005-10-01 00:00:00
abstract::The diaphragm is an essential mammalian skeletal muscle, and defects in diaphragm development are the cause of congenital diaphragmatic hernias (CDHs), a common and often lethal birth defect. The diaphragm is derived from multiple embryonic sources, but how these give rise to the diaphragm is unknown, and, despite the...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.3250
更新日期:2015-05-01 00:00:00
abstract::We sequenced eight melanoma exomes to identify new somatic mutations in metastatic melanoma. Focusing on the mitogen-activated protein (MAP) kinase kinase kinase (MAP3K) family, we found that 24% of melanoma cell lines have mutations in the protein-coding regions of either MAP3K5 or MAP3K9. Structural modeling predict...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng.1041
更新日期:2011-12-25 00:00:00
abstract::The lipodystrophies are a group of disorders characterized by the absence or reduction of subcutaneous adipose tissue. Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase. Additionally, variable degrees of resistance ...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/72807
更新日期:2000-02-01 00:00:00
abstract::Loss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins. Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal su...
journal_title:Nature genetics
pub_type: 杂志文章
doi:10.1038/ng1168
更新日期:2003-06-01 00:00:00