Abstract:
:Multiple physiopathological and clinical conditions trigger skeletal muscle atrophy through the induction of a group of proteins (atrogenes) that includes components of the ubiquitin-proteasome and autophagy-lysosomal systems. Atrogenes are induced by FOXO transcription factors, but their regulation is still not fully understood. Here, we showed that the transcription factor ZEB1, best known for promoting tumor progression, inhibits muscle atrophy and atrogene expression by antagonizing FOXO3-mediated induction of atrogenes. Compared to wild-type counterparts, hindlimb immobilization in Zeb1-deficient mice resulted in enhanced muscle atrophy and higher expression of a number of atrogenes, including Atrogin-1/Fbxo32, MuRF1/Trim63, Ctsl, 4ebp1, Gabarapl1, Psma1 and Nrf2. Likewise, in the C2C12 myogenic cell model, ZEB1 knockdown augmented both myotube diameter reduction and atrogene upregulation in response to nutrient deprivation. Mechanistically, ZEB1 directly represses in vitro and in vivo Fbxo32 and Trim63 promoter transcription in a stage-dependent manner and in a reverse pattern with MYOD1. ZEB1 bound to the Fbxo32 promoter in undifferentiated myoblasts and atrophic myotubes, but not in non-atrophic myotubes, where it is displaced by MYOD1. ZEB1 repressed both promoters through CtBP-mediated inhibition of FOXO3 transcriptional activity. These results set ZEB1 as a new target in therapeutic approaches to clinical conditions causing muscle mass loss.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Ninfali C,Siles L,Darling DS,Postigo Adoi
10.1093/nar/gky835subject
Has Abstractpub_date
2018-11-16 00:00:00pages
10697-10708issue
20eissn
0305-1048issn
1362-4962pii
5124596journal_volume
46pub_type
杂志文章abstract::In Trypanosoma brucei the genes are organised into long polycistronic transcription units and only three promoters for protein-encoding genes and a single terminator have been characterised. These promoters recruit a polI-like RNA polymerase for the transcription units encoding the two major stage-specific antigens of...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.2.597
更新日期:2000-01-15 00:00:00
abstract::The distribution and amount of 5-methylcytosine (5-MeCyt) in DNA was measured for early embryos of mouse strain CF1 (2 to 4 cell stage to blastocyst) and mouse teratocarcinoma cells. In each case, the pattern of methylation was examined by use of the restriction enzymes Hha I and HPA II HPA II, which cut DNA at the si...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/7.8.2369
更新日期:1979-12-20 00:00:00
abstract::Transcriptional repression and activation by nuclear receptors (NRs) are brought about by coregulator complexes. These complexes modify the chromatin environment of target genes and affect the activity of the basal transcription machinery. We have previously implicated the yeast ADA3 protein in transcriptional activat...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.11.2508
更新日期:2002-06-01 00:00:00
abstract::A U3 snoRNA gene isolated from a Chlamydomonas reinhardtii (CRE:) genomic library contains putative pol III-specific transcription signals similar to those of RNA polymerase III-specific small nuclear (sn)RNA genes of higher plants. The 222 nt long CRE: U3 snoRNA was immunoprecipitated by anti-gamma-mpppN antisera, bu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/28.15.2959
更新日期:2000-08-01 00:00:00
abstract::Pulsed field gel electrophoresis was used to determine the location of the tumour necrosis factor (TNF) alpha and beta genes. They were shown to be linked to the HLA-B locus; analogous to their location in mouse, between the complement (class III) region and H-2D. However, the distance between the TNF genes and the cl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.21.8957
更新日期:1987-11-11 00:00:00
abstract::CeR-2 RNA is one of the newly identified Caenorhabditis elegans noncoding RNAs (ncRNAs). The characterization of CeR-2 by RNomic studies has failed to classify it into any known ncRNA family. In this study, we examined the spatiotemporal expression patterns of CeR-2 to gain insight into its function. CeR-2 is expresse...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq335
更新日期:2010-09-01 00:00:00
abstract::The Protein Folding Database (PFD) is a publicly accessible repository of thermodynamic and kinetic protein folding data. Here we describe the first major revision of this work, featuring extensive restructuring that conforms to standards set out by the recently formed International Foldeomics Consortium. The database...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl1007
更新日期:2007-01-01 00:00:00
abstract::A novel method of determining the number of superhelical turns of a covalently-closed plasmid DNA is described. It relies on the determination of the hyperchromicity, and hence the proportion of unstacked basepairs, of a partially heat-denatured sample which co-migrates during electrophoresis with nicked circular dupl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/10.2.525
更新日期:1982-01-22 00:00:00
abstract::Natural oligopeptides may regulate nearly all vital processes. To date, the chemical structures of nearly 6000 oligopeptides have been identified from >1000 organisms representing all the biological kingdoms. We have compiled the known physical, chemical and biological properties of these oligopeptides--whether synthe...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkj008
更新日期:2006-01-01 00:00:00
abstract::Traditional chromatin analysis methods only test one locus at the time or use different templates for each locus, making a standardized analysis of large genomic regions or many co-regulated genes at different loci a difficult task. On the other hand, genome-wide high-resolution mapping of chromatin accessibility empl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp037
更新日期:2009-04-01 00:00:00
abstract::Gene trap vectors developed for genome-wide mutagenesis can be used to study factors governing the expression of exons inserted throughout the genome. For example, entrapment vectors consisting of a partial 3'-terminal exon [i.e. a neomycin resistance gene (Neo), a poly(A) site, but no 3' splice site] were typically e...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkh604
更新日期:2004-05-20 00:00:00
abstract::We have identified cDNAs encoding Mel-N1, the mouse homologue of a human nervous system-specific RNA-binding protein, Hel-N1. Two major mRNA transcripts of Mel-N1 were detected predominantly in the adult mouse brain by Northern blot analysis. To gain insight into the RNA binding specificity of Mel-N1, we performed ite...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.11.2011
更新日期:1996-06-01 00:00:00
abstract::Synthesis and radioiodination of a stannyl oligodeoxyribonucleotide were undertaken to evaluate a gamma ray emitting ODN ligand for thrombus imaging in vivo . Synthesis of the ODN was based on modified automatedbeta-cyanoethyl phosphoramidite chemistry with an organotin nucleoside (dU*) coupled to a thrombin binding a...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.14.2897
更新日期:1997-07-15 00:00:00
abstract::The highly charged DNA chain may be either in an extended conformation, the coil, or condensed into a highly dense and ordered structure, the toroid. The transition, also called collapse of the chain, can be triggered in different ways, for example by changing the ionic conditions of the solution. We observe individua...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv1494
更新日期:2016-02-18 00:00:00
abstract::Non-structural protein 3 (NS3) of hepatitis C virus (HCV) has two distinct activities, protease and helicase, which are essential for HCV proliferation. In previous work, we obtained RNA aptamers (G9-I, II and III) which specifically bound the NS3 protease domain (DeltaNS3), efficiently inhibiting protease activity in...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkg291
更新日期:2003-04-01 00:00:00
abstract::We have examined the ability of a cationic planar chromophore, ethidium bromide, to intercalate into a short, defined triple helix. Using UV absorption, fluorescence spectroscopy and a gel retardation assay we demonstrate that ethidium bromide is able to bind to a triple helix with a lower affinity than to the corresp...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.7.1521
更新日期:1991-04-11 00:00:00
abstract::Sgs1 is a member of the RecQ family of DNA helicases, which have been implicated in genomic stability, cancer and ageing. Srs2 is another DNA helicase that shares several phenotypic features with Sgs1 and double sgs1srs2 mutants have a severe synthetic growth phenotype. This suggests that there may be functional overl...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.5.1103
更新日期:2002-03-01 00:00:00
abstract::Genetic screens in Saccharomyces cerevisiae have identified the roles of ribosome components, tRNAs and translation factors in translational fidelity. These screens rely on the suppression of altered start codons, nonsense codons or frameshift mutations in genes involved in amino acid or nucleotide metabolism. Many of...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki765
更新日期:2005-08-12 00:00:00
abstract::The UCSC Genome Browser (https://genome.ucsc.edu) provides a web interface for exploring annotated genome assemblies. The assemblies and annotation tracks are updated on an ongoing basis-12 assemblies and more than 28 tracks were added in the past year. Two recent additions are a display of CRISPR/Cas9 guide sequences...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkx1020
更新日期:2018-01-04 00:00:00
abstract::PALI (release 1.2) contains three-dimensional (3-D) structure-dependent sequence alignments as well as structure-based phylogenetic trees of homologous protein domains in various families. The data set of homologous protein structures has been derived by consulting the SCOP database (release 1.50) and the data set com...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/29.1.61
更新日期:2001-01-01 00:00:00
abstract::The far upstream region of herpes simplex virus (HSV) immediate early (IE) gene 3 has previously been shown to increase gene expression in an enhancer-like manner, and to contain sequences which respond to stimulation of transcription by a virion polypeptide, Vmw65. To analyse the specific DNA sequences which mediate ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/14.2.929
更新日期:1986-01-24 00:00:00
abstract::Recently, a few Na+-specific RNA-cleaving DNAzymes were reported, where nucleobases are likely to play critical roles in catalysis. The NaA43 and NaH1 DNAzymes share the same 16-nt Na+-binding motif, but differ in one or two nucleotides in a small catalytic loop. Nevertheless, they display an opposite pH-dependency, i...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkz578
更新日期:2019-09-05 00:00:00
abstract::The International Mouse Phenotyping Consortium (IMPC) web portal (http://www.mousephenotype.org) provides the biomedical community with a unified point of access to mutant mice and rich collection of related emerging and existing mouse phenotype data. IMPC mouse clinics worldwide follow rigorous highly structured and ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt977
更新日期:2014-01-01 00:00:00
abstract::Infrared spectroscopy was used to identify hydration-sensitive structural differences between single- stranded phosphorothioate (PS) and phosphodiester (PO) oligodeoxyribonucleotides. Spectra were recorded in the mid-infrared region, 500-1800 cm-1, at relative humidities between 0 and 98%; the PS and PO spectra are su...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/24.16.3261
更新日期:1996-08-15 00:00:00
abstract::A downstream G-rich sequence (GRS), GGGGGAGGUGUGGG, has been previously shown to influence the efficiency of 3' end processing of the SV40 late polyadenylation signal. We have now defined several important parameters for GRS-mediated polyadenylation. The ability of the GRS to influence 3' end processing efficiency was...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/23.9.1625
更新日期:1995-05-11 00:00:00
abstract::Trinucleotide repeat (TNR) expansions cause at least 17 heritable neurological diseases, including Huntington's disease. Expansions are thought to arise from abnormal processing of TNR DNA by specific trans-acting proteins. For example, the DNA repair complex MutSβ (MSH2-MSH3 heterodimer) is required in mice for on-go...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks810
更新日期:2012-11-01 00:00:00
abstract::Electrophoretic mobility shift assays (EMSA) were used to define the regions of the INO1 promoter that interact with factors present in extracts prepared from the yeast, Saccharomyces cerevisae. These experiments identified three different types of protein:DNA complexes that assemble with the INO1 promoter. Formation ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/19.14.3987
更新日期:1991-07-25 00:00:00
abstract::Hepatitis B viruses, or hepadnaviruses, are small DNA-containing viruses that replicate through reverse transcription. Their prototype, HBV, causes severe liver disease in humans. The hepadnaviral P protein is an unusual reverse transcriptase (RT) that initiates DNA synthesis by host-factor-dependent protein priming o...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/30.7.1679
更新日期:2002-04-01 00:00:00
abstract::In the virion core of retroviruses, the genomic RNA is tightly associated with nucleocapsid (NC) protein molecules, forming the nucleocapsid structure. NC protein, a highly basic protein with two zinc fingers, is indispensable for RNA dimerization, encapsidation and the initiation of reverse transcription in avian, mu...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/21.4.831
更新日期:1993-02-25 00:00:00
abstract::Human minisatellite probes cross-hybridize to mouse DNA and detect multiple variable loci. The resulting DNA "fingerprints" vary substantially between inbred strains but relatively little within an inbred strain. By studying the segregation of variable DNA fragments in BXD recombinant inbred strains of mice, at least ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/15.7.2823
更新日期:1987-04-10 00:00:00