Abstract:
:Silencing of multiple cancer-related genes is associated with de novo methylation of linked CpG islands. Additionally, bivalent histone modification profiles characterized by the juxtaposition of active and inactive histone marks have been observed in genes that become hypermethylated in cancer. It is unknown how these ambiguous epigenetic states are maintained and how they interrelate with adjacent genomic regions with different epigenetic landscapes. Here, we present the analysis of a set of neighboring genes, including many frequently silenced in colon cancer cells, in a chromosomal region at 5q35.2 spanning 1.25 Mb. Promoter DNA methylation occurs only at genes maintained at a low transcriptional state and is characterized by the presence of bivalent histone marks, namely trimethylation of lysines 4 and 27 in histone 3. Chemically induced hyperacetylation and DNA demethylation lead to up-regulation of silenced genes in this locus yet do not resolve bivalent domains into a domain-wide active chromatin conformation. In contrast, active genes in the region become down-regulated after drug treatment, accompanied by a partial loss of chromatin domain boundaries and spreading of the inactive histone mark trimethylated lysine 27 in histone 3. Our results demonstrate that bivalent domains mark the promoters of genes that will become DNA methylated in adult tumor cells to enforce transcriptional silence. These bivalent domains not only remain upon drug induced gene reactivation, but also spread over adjacent CpG islands. These results may have important implications in understanding and managing epigenetic therapies of cancer.
journal_name
Proc Natl Acad Sci U S Aauthors
Rodriguez J,Muñoz M,Vives L,Frangou CG,Groudine M,Peinado MAdoi
10.1073/pnas.0810133105subject
Has Abstractpub_date
2008-12-16 00:00:00pages
19809-14issue
50eissn
0027-8424issn
1091-6490pii
0810133105journal_volume
105pub_type
杂志文章abstract::Ubiquitin C-terminal hydrolase-L1 (UCHL1), a neuron-specific de-ubiquitinating enzyme, is one of the most abundant proteins in the brain. We describe three siblings from a consanguineous union with a previously unreported early-onset progressive neurodegenerative syndrome featuring childhood onset blindness, cerebella...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1222732110
更新日期:2013-02-26 00:00:00
abstract::Social media sites are rapidly becoming one of the most important forums for public deliberation about advocacy issues. However, social scientists have not explained why some advocacy organizations produce social media messages that inspire far-ranging conversation among social media users, whereas the vast majority o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1607151113
更新日期:2016-10-18 00:00:00
abstract::Controlling topological defects in 3D liquid crystal phases is a crucial element in the development of novel devices, from blue-phase displays to passive biochemical sensors. However, it remains challenging to realize the 3D topological conditions necessary to robustly and arbitrarily direct the formation of defects. ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1214708109
更新日期:2013-01-02 00:00:00
abstract::Peroxisome proliferators (PP) induce a highly predictable pleiotropic response in rat and mouse liver that is characterized by hepatomegaly, increase in peroxisome number in hepatocytes, and induction of certain peroxisomal enzymes. The PP-binding protein (PPbP) was purified from rat liver cytosol by a two-step proced...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.84.15.5242
更新日期:1987-08-01 00:00:00
abstract::Genomic islands, large potentially mobile regions of bacterial chromosomes, are a major contributor to bacteria evolution. Here, we investigated the fitness cost and phenotypic differences between the bacterium Pseudomonas aeruginosa PAO1 and a derivative carrying one integrated copy of the clc element, a 103-kb genom...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0801269105
更新日期:2008-05-13 00:00:00
abstract::A series of spontaneous suppressors to the temperature-sensitive phenotype of the single-stranded DNA-binding protein mutation ssb-1 were isolated. A genomic library of EcoRI fragments from one of these suppressor strains was prepared by using pBR325 as the cloning vector. A 10.0-kilobase class of inserts was identifi...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.85.11.3767
更新日期:1988-06-01 00:00:00
abstract::A 978-base-pair gene that encodes thymidylate synthase (TS; 5,10-methylenetetrahydrofolate:dUMP C-methyltransferase, EC 2.1.1.45) from Lactobacillus casei has been synthesized and inserted into Escherichia coli expression vectors. The DNA sequence contains 35 unique restriction sites that are located an average of 28 ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.2.633
更新日期:1990-01-01 00:00:00
abstract::When Drosophila melanogaster embryos were ligated at very early stages of nuclear multiplication (45-60 min after egg deposition) for the entire period of embryogenesis, egg fragments of variable sizes were able to continue development up to the hatching stage. These ligated embryos differentiated larval structures; a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.74.5.2050
更新日期:1977-05-01 00:00:00
abstract::The N-terminal domain of HIV-1 integrase contains a pair of His and Cys residues (the HHCC motif) that are conserved among retroviral integrases. Although His and Cys residues are often involved in binding zinc, the HHCC motif does not correspond to any recognized class of zinc binding domain. We have investigated the...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.24.13659
更新日期:1996-11-26 00:00:00
abstract::Production of amyloid-beta protein (Abeta) is initiated by a beta-secretase that cleaves the Abeta precursor protein (APP) at the N terminus of Abeta (the beta site). A recently identified aspartyl protease, BACE, cleaves the beta site and at residue 11 within the Abeta region of APP. Here we show that BACE2, a BACE h...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.160115697
更新日期:2000-08-15 00:00:00
abstract::Mucosa-associated lymphoid tissue (MALT) lymphoma is the most common extranodal lymphoid cell neoplasia; it frequently follows chronic bacteria-induced inflammation in various tissues. MALT lymphomas are characterized genetically by the t(11;18)(q21;q21) translocation, which yields chimeric transcripts encoding struct...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0402415101
更新日期:2004-06-15 00:00:00
abstract::When the lactose (lac) permease of Escherichia coli is expressed from the lac promoter at relatively low rates, deletion of amino acid residues 2-8 (delta 7) or 2-9 (delta 8) from the hydrophilic N terminus has a relatively minor effect on the ability of the permease to catalyze active lactose transport. Activity is e...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.89.8.3180
更新日期:1992-04-15 00:00:00
abstract::We have previously shown that lymphoblasts alloactivated in vitro acquire the capacity of stimulating the autologous mixed lymphocyte response. This response is anti-idiotypic in nature because lymphocytes so primed display accelerated memory responses only when restimulated by autologous lymphoblasts that have been a...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.3.830
更新日期:1983-02-01 00:00:00
abstract::Cloned DNA probes containing genes coding for the large subunit of ribulose-1,5-bisphosphate carboxylase (rbcA) of corn and of Chlamydomonas were used to identify, by heterologous hybridization, DNA fragments from Anabaena 7120 carrying the corresponding gene sequence. The same probes were used to isolate, from a reco...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.80.7.1835
更新日期:1983-04-01 00:00:00
abstract::The binding of thyroid hormone to the thyroid hormone receptor (TR) mediates important physiological effects. However, the transcriptional effects of TR mediated by the thyroid response element (TRE) cannot explain many actions of thyroid hormone. We postulate that TR can initiate rapid, non-TRE-mediated effects in th...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0601600103
更新日期:2006-09-19 00:00:00
abstract::The proinflammatory and catabolic cytokine IL-1β has been implicated in the pathogenesis of osteoarthritis (OA) by mediating synovial inflammation and cartilage degeneration. Although synovial macrophages are suggested to be the source of IL-1β, the mechanism remains unclear. Ectopic deposition of hydroxyapatite (HA) ...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1111101108
更新日期:2011-09-06 00:00:00
abstract::We have studied the in vivo signaling mechanisms involved in nociceptin/orphanin FQ (Noci)-induced pain responses by using a flexor-reflex paradigm. Noci was 10,000 times more potent than substance P (SP) in eliciting flexor responses after intraplantar injection into the hind limb of mice, but the action of Noci seem...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.95.18.10949
更新日期:1998-09-01 00:00:00
abstract::Hepatic alpha 2u-globulin protein and RNA levels are under developmental and complex multihormonal control. The present studies directly evaluate the degree to which this regulation is transcriptional. alpha 2u-Globulin transcription was determined by measuring nuclear runoff RNA in vitro, and tissue alpha 2u-globulin...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.82.9.2579
更新日期:1985-05-01 00:00:00
abstract::In most organisms, light plays a key role in the synchronization of the circadian timing system with the environmental day-night cycle. Light pulses that phase-shift the circadian clock also induce the expression of period (per) genes in vertebrates. Here, we report the cloning of a zebrafish per gene, zfper4, which i...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0305436101
更新日期:2004-03-23 00:00:00
abstract::Injection of exogenous mRNA purified from various tissue preparations into cellular translation systems such as Xenopus oocytes has allowed expression of complex proteins (e.g., receptors for neurotransmitters). No evidence for expression of injected exogenous mRNA, however, has been reported in terminally differentia...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.87.20.7844
更新日期:1990-10-01 00:00:00
abstract::Sea urchins are a major component of recent marine communities where they exert a key role as grazers and benthic predators. However, their impact on past marine organisms, such as crinoids, is hard to infer in the fossil record. Analysis of bite mark frequencies on crinoid columnals and comprehensive genus-level dive...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 历史文章,杂志文章
doi:10.1073/pnas.1201573109
更新日期:2012-05-01 00:00:00
abstract::A sensitive target binding assay has recently been shown to detect natural killer (NK) cells in the mouse. Preincubation of NK cells with detergent-solubilized cell-surface proteins of YAC lymphoma cells prevented subsequent binding to intact YAC targets. The NK target structures (NK-TS) consisted of three molecular s...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.76.3.1405
更新日期:1979-03-01 00:00:00
abstract::Lewis base catalyzed bromo- and iodolactonization reactions have been developed and the effects of catalyst structure on rate and cyclization selectivity have been systematically explored. The effects of substrate structure on halolactonization reactions and the interaction of those effects with the effects of catalys...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1005296107
更新日期:2010-11-30 00:00:00
abstract::Protein tyrosine phosphatase (PTP)σ (PTPRS) was shown previously to be associated with susceptibility to inflammatory bowel disease (IBD). PTPσ(-/-) mice exhibit an IBD-like phenotype in the intestine and show increased susceptibility to acute models of murine colitis. However, the function of PTPσ in the intestine is...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1315017111
更新日期:2014-01-14 00:00:00
abstract::The heptadecapeptide orphanin FQ (OFQ) is a recently discovered neuropeptide that exhibits structural features reminiscent of the opioid peptides and that is an endogenous ligand to a G protein-coupled receptor sequentially related to the opioid receptors. We have cloned both the human and rat cDNAs encoding the OFQ p...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.93.16.8677
更新日期:1996-08-06 00:00:00
abstract::It has been shown that [35S]methionine is incorporated into the [Met]enkephalin sequences of a 22,000-dalton enkephalin-containing protein in the adrenal medulla. Pulse-chase experiments indicate that label is incorporated into the large polypeptide before it appears in free [Met]enkephalin and a smaller [Met]enkephal...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.11.6889
更新日期:1980-11-01 00:00:00
abstract::Certain mutations at the glaB locus result in the failure to fully derepress glutamine synthetase [L-glutamate:ammonia ligase (ADP-forming), EC 6.3.1.2] and to convert it to the active nonadenylylated form in response to nitrogen limitation. In these mutants the PII regulatory protein is altered such that it cannot be...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.77.5.2636
更新日期:1980-05-01 00:00:00
abstract::Certain models of spoken-language processing, like those for many other perceptual and cognitive processes, posit continuous uptake of sensory input and dynamic competition between simultaneously active representations. Here, we provide compelling evidence for this continuity assumption by using a continuous response,...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.0503903102
更新日期:2005-07-19 00:00:00
abstract::Enterohemorrhagic Escherichia coli O157 is one of the leading worldwide public health concerns, causing large outbreaks of hemorrhagic colitis as well as numerous small outbreaks and sporadic cases. The variability of restriction enzyme-digestion patterns of O157 genomes, which is widely used to distinguish strains in...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.262441699
更新日期:2002-12-24 00:00:00
abstract::Despite the success statistical physics has enjoyed at predicting the properties of materials for given parameters, the inverse problem, identifying which material parameters produce given, desired properties, is only beginning to be addressed. Recently, several methods have emerged across disciplines that draw upon o...
journal_title:Proceedings of the National Academy of Sciences of the United States of America
pub_type: 杂志文章
doi:10.1073/pnas.1509316112
更新日期:2016-01-05 00:00:00