Abstract:
:Increasing evidence indicates that active DNA demethylation is involved in several processes in mammals, resulting in developmental stage-specificity and cell lineage-specificity. The recently discovered Ten-Eleven Translocation (TET) dioxygenases are accepted to be involved in DNA demethylation by initiating 5-mC oxidation. Aberrant DNA methylation profiles are associated with many diseases. For example in cancer, hypermethylation results in silencing of tumor suppressor genes. Such silenced genes can be re-expressed by epigenetic drugs, but this approach has genome-wide effects. In this study, fusions of designer DNA binding domains to TET dioxygenase family members (TET1, -2 or -3) were engineered to target epigenetically silenced genes (ICAM-1, EpCAM). The effects on targeted CpGs' methylation and on expression levels of the target genes were assessed. The results indicated demethylation of targeted CpG sites in both promoters for targeted TET2 and to a lesser extent for TET1, but not for TET3. Interestingly, we observed re-activation of transcription of ICAM-1. Thus, our work suggests that we provided a mechanism to induce targeted DNA demethylation, which facilitates re-activation of expression of the target genes. Furthermore, this Epigenetic Editing approach is a powerful tool to investigate functions of epigenetic writers and erasers and to elucidate consequences of epigenetic marks.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Chen H,Kazemier HG,de Groote ML,Ruiters MH,Xu GL,Rots MGdoi
10.1093/nar/gkt1019subject
Has Abstractpub_date
2014-02-01 00:00:00pages
1563-74issue
3eissn
0305-1048issn
1362-4962pii
gkt1019journal_volume
42pub_type
杂志文章abstract::BioModels Database (http://www.ebi.ac.uk/biomodels/), part of the international initiative BioModels.net, provides access to published, peer-reviewed, quantitative models of biochemical and cellular systems. Each model is carefully curated to verify that it corresponds to the reference publication and gives the proper...
journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gni179
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abstract::DNA assembly allows individual DNA constructs or libraries to be assembled quickly and reliably. Most methods are either: (i) Modular, easily scalable and suitable for combinatorial assembly, but leave undesirable 'scar' sequences; or (ii) bespoke (non-modular), scarless but less suitable for construction of combinato...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gky1182
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abstract::A mass spectral method is described for the detection and identification of unusual nucleotide residues present in DNAs. Analysis by this method of intact, underivatized DNA from salmon sperm, calf thymus, mouse L-cells, wheat germ, M. lysodeikticus, E. Coli, and the bacteriophages 0X-174, fd, and lamda, yields diagno...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/3.11.2959
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkn524
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp1153
更新日期:2010-04-01 00:00:00
abstract::Transposable elements (TEs) and their relics play major roles in genome evolution. However, mobilization of TEs is usually deleterious and strongly repressed. In plants and mammals, this repression is typically associated with DNA methylation, but the relationship between this epigenetic mark and TE sequences has not ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkr324
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkq334
更新日期:2010-09-01 00:00:00
abstract::Ribosome biogenesis is fundamental for cellular life, but surprisingly little is known about the underlying pathway. In eukaryotes a comprehensive collection of experimentally verified ribosome biogenesis factors (RBFs) exists only for Saccharomyces cerevisiae. Far less is known for other fungi, animals or plants, and...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkt1137
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks1085
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkp097
更新日期:2009-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/nar/9.12.2777
更新日期:1981-06-25 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkv901
更新日期:2015-10-15 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::IntAct is an open source database and software suite for modeling, storing and analyzing molecular interaction data. The data available in the database originates entirely from published literature and is manually annotated by expert biologists to a high level of detail, including experimental methods, conditions and ...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl958
更新日期:2007-01-01 00:00:00
abstract::The 5' portions and flanking sequences of genes encoding types 1, 12, 24, and 6 M proteins were compared. Although the DNA sequences encoding the amino-termini of the mature M proteins had no obvious similarity, upstream sequences, and those encoding the signal peptides (leader sequences) of the four M protein genes h...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/16.10.4667
更新日期:1988-05-25 00:00:00
abstract::Most mutations in cancer genomes occur in the non-coding regions with unknown impact on tumor development. Although the increase in the number of cancer whole-genome sequences has revealed numerous putative non-coding cancer drivers, their information is dispersed across multiple studies making it difficult to underst...
journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkaa915
更新日期:2021-01-08 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
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/10.21.6919
更新日期:1982-11-11 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:2014-11-10 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gki486
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/25.8.1516
更新日期:1997-04-15 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gkl868
更新日期:2007-01-01 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:1989-03-25 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
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journal_title:Nucleic acids research
pub_type: 杂志文章
doi:10.1093/nar/gks822
更新日期:2012-11-01 00:00:00
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journal_title:Nucleic acids research
pub_type: 杂志文章
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更新日期:2014-07-01 00:00:00