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http://dx.doi.org/10.18419/opus-14348
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DC Element | Wert | Sprache |
---|---|---|
dc.contributor.author | Albrecht, Claudia | - |
dc.contributor.author | Rajaram, Nivethika | - |
dc.contributor.author | Broche, Julian | - |
dc.contributor.author | Bashtrykov, Pavel | - |
dc.contributor.author | Jeltsch, Albert | - |
dc.date.accessioned | 2024-05-10T10:17:44Z | - |
dc.date.available | 2024-05-10T10:17:44Z | - |
dc.date.issued | 2024 | de |
dc.identifier.issn | 2073-4425 | - |
dc.identifier.other | 1888536543 | - |
dc.identifier.uri | http://nbn-resolving.de/urn:nbn:de:bsz:93-opus-ds-143678 | de |
dc.identifier.uri | http://elib.uni-stuttgart.de/handle/11682/14367 | - |
dc.identifier.uri | http://dx.doi.org/10.18419/opus-14348 | - |
dc.description.abstract | DNA methylation is critically involved in the regulation of chromatin states and cell-type-specific gene expression. The exclusive expression of imprinted genes from either the maternal or the paternal allele is regulated by allele-specific DNA methylation at imprinting control regions (ICRs). Aberrant DNA hyper- or hypomethylation at the ICR1 of the H19/IGF2 imprinting locus is characteristic for the imprinting disorders Beckwith-Wiedemann syndrome (BWS) and Silver-Russell syndrome (SRS), respectively. In this paper, we performed epigenome editing to induce targeted DNA demethylation at ICR1 in HEK293 cells using dCas9-SunTag and the catalytic domain of TET1. 5-methylcytosine (5mC) levels at the target locus were reduced up to 90% and, 27 days after transient transfection, >60% demethylation was still observed. Consistent with the stable demethylation of CTCF-binding sites within the ICR1, the occupancy of the DNA methylation-sensitive insulator CTCF protein increased by >2-fold throughout the 27 days. Additionally, the H19 expression was increased by 2-fold stably, while IGF2 was repressed though only transiently. Our data illustrate the ability of epigenome editing to implement long-term changes in DNA methylation at imprinting control regions after a single transient treatment, potentially paving the way for therapeutic epigenome editing approaches in the treatment of imprinting disorders. | en |
dc.description.sponsorship | DFG | de |
dc.description.sponsorship | BW Foundation | de |
dc.language.iso | en | de |
dc.relation.uri | doi:10.3390/genes15010080 | de |
dc.rights | info:eu-repo/semantics/openAccess | de |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | de |
dc.subject.ddc | 540 | de |
dc.title | Locus-specific and stable DNA demethylation at the H19/IGF2 ICR1 by epigenome editing using a dCas9-SunTag system and the catalytic domain of TET1 | en |
dc.type | article | de |
dc.date.updated | 2024-04-25T13:24:24Z | - |
ubs.fakultaet | Chemie | de |
ubs.institut | Institut für Biochemie und Technische Biochemie | de |
ubs.publikation.seiten | 15 | de |
ubs.publikation.source | Genes 15 (2024), No. 80 | de |
ubs.publikation.typ | Zeitschriftenartikel | de |
Enthalten in den Sammlungen: | 03 Fakultät Chemie |
Dateien zu dieser Ressource:
Datei | Beschreibung | Größe | Format | |
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genes-15-00080-v2.pdf | Artikel | 2,31 MB | Adobe PDF | Öffnen/Anzeigen |
genes-15-00080-s001.zip | Supplement | 1,01 MB | Unknown | Öffnen/Anzeigen |
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