Abstract：
:The Polycomb repressive complexes PRC1 and PRC2 maintain embryonic stem cell (ESC) pluripotency by silencing lineage-specifying developmental regulator genes. Emerging evidence suggests that Polycomb complexes act through controlling spatial genome organization. We show that PRC1 functions as a master regulator of mouse ESC genome architecture by organizing genes in three-dimensional interaction networks. The strongest spatial network is composed of the four Hox gene clusters and early developmental transcription factor genes, the majority of which contact poised enhancers. Removal of Polycomb repression leads to disruption of promoter-promoter contacts in the Hox gene network. In contrast, promoter-enhancer contacts are maintained in the absence of Polycomb repression, with accompanying widespread acquisition of active chromatin signatures at network enhancers and pronounced transcriptional upregulation of network genes. Thus, PRC1 physically constrains developmental transcription factor genes and their enhancers in a silenced but poised spatial network. We propose that the selective release of genes from this spatial network underlies cell fate specification during early embryonic development.
journal_name
Nat Genetjournal_title
Nature geneticsauthors
Schoenfelder S,Sugar R,Dimond A,Javierre BM,Armstrong H,Mifsud B,Dimitrova E,Matheson L,Tavares-Cadete F,Furlan-Magaril M,Segonds-Pichon A,Jurkowski W,Wingett SW,Tabbada K,Andrews S,Herman B,LeProust E,Osborne CS,Kosedoi
10.1038/ng.3393subject
Has Abstractpub_date
2015-10-01 00:00:00pages
1179-1186issue
10eissn
1061-4036issn
1546-1718journal_volume
47pub_type
杂志文章相关文献
NATURE GENETICS文献大全abstract：:We performed a whole-genome association analysis of lung tumor susceptibility using dense SNP maps ( approximately 1 SNP per 20 kb) in inbred mice. We reproduced the pulmonary adenoma susceptibility 1 (Pas1) locus identified in previous linkage studies and further narrowed this quantitative trait locus (QTL) to a regi...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng1849
更新日期：2006-08-01 00:00:00
abstract：:Accumulation of genetic incompatibilities within species can lead to reproductive isolation and, potentially, speciation. In this study, we show that allelic variation at SRF3 (Strubbelig Receptor Family 3), encoding a receptor-like kinase, conditions the occurrence of incompatibility between Arabidopsis thaliana acce...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng.704
更新日期：2010-12-01 00:00:00
abstract：:The basic helix-loop-helix (bHLH) transcription factors, Hand1 and Hand2 (refs 1,2), also called eHand/Hxt/Thing1 and dHand/Hed/Thing2 (refs 3,4), respectively, are expressed in the heart and certain neural-crest derivatives during embryogenesis. In addition, Hand1 is expressed in extraembryonic membranes, whereas Han...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng0398-266
更新日期：1998-03-01 00:00:00
abstract：:To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant ex...
journal_title：Nature genetics
pub_type： 杂志文章,meta分析
doi：10.1038/ng.2897
更新日期：2014-03-01 00:00:00
abstract：:Ocular retardation (or) is a murine eye mutation causing microphthalmia, a thin hypocellular retina and optic nerve aplasia. Here we show that mice carrying the OrJ allele have a premature stop codon in the homeobox of the Chx10 gene, a gene expressed at high levels in uncommitted retinal progenitor cells and mature b...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng0496-376
更新日期：1996-04-01 00:00:00
abstract：:Polymicrogyria is a relatively common but poorly understood defect of cortical development characterized by numerous small gyri and a thick disorganized cortical plate lacking normal lamination. Here we report de novo mutations in a beta-tubulin gene, TUBB2B, in four individuals and a 27-gestational-week fetus with bi...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng.380
更新日期：2009-06-01 00:00:00
abstract：:The DiGeorge/velocardiofacial syndrome (DGS/VCFS) is a relatively common human disorder, usually associated with deletions of chromosome 22q11. The genetic basis for the wide range of developmental anomalies in the heart, glands and facial structures has been elusive. We have investigated the potential role of one can...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/85845
更新日期：2001-03-01 00:00:00
abstract：:Autosomal dominant polycystic kidney disease (ADPKD) describes a group of at least three genetically distinct disorders with almost identical clinical features that collectively affects 1:1,000 of the population. Affected individuals typically develop large cystic kidneys and approximately one half develop end-stage r...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng0697-179
更新日期：1997-06-01 00:00:00
abstract：:Friedreich's ataxia is due to loss of function mutations in the gene encoding frataxin (FRDA). Frataxin is a protein of unknown function. In situ hybridization analyses revealed that mouse frataxin expression correlates well with the main site of neurodegeneration, but the expression pattern is broader than expected f...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng0897-345
更新日期：1997-08-01 00:00:00
abstract：:Desmin-related myopathies (DRM) are inherited neuromuscular disorders characterized by adult onset and delayed accumulation of aggregates of desmin, a protein belonging to the type III intermediate filament family, in the sarcoplasma of skeletal and cardiac muscles. In this paper, we have mapped the locus for DRM in a...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/1765
更新日期：1998-09-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Nature genetics
pub_type： 已发布勘误
doi：10.1038/s41588-020-0588-3
更新日期：2020-04-01 00:00:00
abstract：:Altering cytosine methylation by genetic means leads to a variety of developmental defects in mice, plants and fungi. Deregulation of cytosine methylation also has a role in human carcinogenesis. In some cases, these defects have been tied to the inheritance of epigenetic alterations (such as chromatin imprints and DN...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/8803
更新日期：1999-05-01 00:00:00
abstract：:Most errors that arise during DNA replication can be corrected by DNA polymerase proofreading or by post-replication mismatch repair (MMR). Inactivation of both mutation-avoidance systems results in extremely high mutability that can lead to error catastrophe. High mutability and the likelihood of cancer can be caused...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng1172
更新日期：2003-07-01 00:00:00
abstract：:Type 1 diabetes (T1D) is a common autoimmune disorder that arises from the action of multiple genetic and environmental risk factors. We report the findings of a genome-wide association study of T1D, combined in a meta-analysis with two previously published studies. The total sample set included 7,514 cases and 9,045 ...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng.381
更新日期：2009-06-01 00:00:00
abstract：:During evolution different genes evolve at unequal rates, reflecting the varying functional constraints on phenotype. An important contributor to this variation is genetic buffering, which reduces the potential detrimental effects of mutations. We studied whether gene duplication and redundant metabolic networks affec...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng945
更新日期：2002-09-01 00:00:00
abstract：:Autosomal dominant retinal vasculopathy with cerebral leukodystrophy is a microvascular endotheliopathy with middle-age onset. In nine families, we identified heterozygous C-terminal frameshift mutations in TREX1, which encodes a 3'-5' exonuclease. These truncated proteins retain exonuclease activity but lose normal p...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng2082
更新日期：2007-09-01 00:00:00
abstract：:The hedgehog family of morphogens are regulators of cell proliferation, differentiation and cell-cell communication. These morphogens have been shown to have important roles in organogenesis, spermatogenesis, stem cell maintenance and oncogenesis. Indian hedgehog (encoded by Ihh) has been shown to be expressed in the ...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng1874
更新日期：2006-10-01 00:00:00
abstract：:We have carried out automated extraction of explicit and implicit biomedical knowledge from publicly available gene and text databases to create a gene-to-gene co-citation network for 13,712 named human genes by automated analysis of titles and abstracts in over 10 million MEDLINE records. The associations between gen...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng0501-21
更新日期：2001-05-01 00:00:00
abstract：:The organophosphate cholinesterase inhibitor paraoxon is hydrolysed by serum paraoxonase/arylesterase. A genetic polymorphism of paraoxonase (PON) activity which determines high versus low paraoxon hydrolysis in human populations, may determine sensitivity to parathion poisoning. We demonstrate that arginine at positi...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng0193-73
更新日期：1993-01-01 00:00:00
abstract：:Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing b...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng.3878
更新日期：2017-07-01 00:00:00
abstract：:A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 x 10(-11), odds ratio (OR...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng.627
更新日期：2010-08-01 00:00:00
abstract：:The mammalian TET enzymes catalyze DNA demethylation. While they have been intensely studied as major epigenetic regulators, little is known about their physiological roles and the extent of functional redundancy following embryo implantation. Here we define non-redundant roles for TET1 at an early postimplantation st...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng.3868
更新日期：2017-07-01 00:00:00
abstract：:We have genetically retrieved, resurrected and performed detailed structure-function analyses on authentic woolly mammoth hemoglobin to reveal for the first time both the evolutionary origins and the structural underpinnings of a key adaptive physiochemical trait in an extinct species. Hemoglobin binds and carries O(2...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng.574
更新日期：2010-06-01 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：:In the version of this article originally published, a box was misplaced in Fig. 1. The error has been corrected in the HTML and PDF versions of the article. ...
journal_title：Nature genetics
pub_type： 杂志文章,已发布勘误
doi：10.1038/s41588-018-0137-5
更新日期：2018-08-01 00:00:00
abstract：:Schwannomas are common peripheral nerve sheath tumors that can cause debilitating morbidities. We performed an integrative analysis to determine genomic aberrations common to sporadic schwannomas. Exome sequence analysis with validation by targeted DNA sequencing of 125 samples uncovered, in addition to expected NF2 d...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng.3688
更新日期：2016-11-01 00:00:00
abstract：:Methylation of cytosines within the sequence CpG is essential for mouse development and has been linked to transcriptional suppression in vertebrate systems. Methyl-CpG binding proteins (MeCPs) 1 and 2 bind preferentially to methylated DNA and can inhibit transcription. The gene for MeCP2 has been cloned and a methyl-...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng0797-256
更新日期：1997-07-01 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：:Protein tyrosine phosphorylation plays a key role in regulating eukaryotic cell proliferation and differentiation. Genetic analysis in invertebrates has been invaluable for dissecting the signalling events downstream of receptor tyrosine kinases (RTKs). We have used this approach in mammals to analyse the interactions...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng0796-309
更新日期：1996-07-01 00:00:00
abstract：:Measurements of erythrocytes within the blood are important clinical traits and can indicate various hematological disorders. We report here genome-wide association studies (GWAS) for six erythrocyte traits, including hemoglobin concentration (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemo...
journal_title：Nature genetics
pub_type： 杂志文章
doi：10.1038/ng.466
更新日期：2009-11-01 00:00:00
