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dc.contributor.authorArroyo-Lopez, Maria C
dc.contributor.authorHastert, Florian D.
dc.contributor.authorZhadan, Andreas
dc.contributor.authorSchelter, Florian
dc.contributor.authorZimbelmann, Susanne
dc.contributor.authorRausch, Cathia
dc.contributor.authorLudwig, Anne K.
dc.contributor.authorCarell, Thomas
dc.contributor.authorCardoso, M. Cristina
dc.date.accessioned2021-07-20T12:34:24Z
dc.date.available2021-07-20T12:34:24Z
dc.date.issued2021-07
dc.identifier.urihttps://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/2873
dc.descriptionOxidation of the epigenetic DNA mark 5-methylcytosine by Tet dioxygenases is an established route to diversify the epigenetic information, modulate gene expression and overall cellular (patho-)physiology. Here, we demonstrate that Tet1 and its short isoform Tet1s exhibit distinct nuclear localization during DNA replication resulting in aberrant cytosine modification levels in human and mouse cells. We show that Tet1 is tethered away from heterochromatin via its zinc finger domain, which is missing in Tet1s allowing its targeting to these regions. We find that Tet1s interacts with and is ubiquitinated by CRL4(VprBP). The ubiquitinated Tet1s is then recognized by Uhrf1 and recruited to late replicating heterochromatin. This leads to spreading of 5-methylcytosine oxidation to heterochromatin regions, LINE 1 activation and chromatin decondensation. In summary, we elucidate a novel dual regulation mechanism of Tet1, contributing to the understanding of how epigenetic information can be diversified by spatio-temporal directed Tet1 catalytic activity.en_US
dc.language.isoenen_US
dc.rightsCreative Commons Attribution-NonCommercial 4.0
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.subjectDNA modificationsen_US
dc.subjectDNA replicationen_US
dc.subjectFluorescence microscopyen_US
dc.subjectHeterochromatinen_US
dc.subjectImage analysisen_US
dc.subjectMethylcytosineen_US
dc.subjectUbiquitinationen_US
dc.subject.classification201-03 Zellbiologieen_US
dc.subject.ddc570
dc.titleIsoform-specific and ubiquitination dependent recruitment of Tet1 to replicating heterochromatin causes aberrant methylcytosine oxidationen_US
dc.typeDataseten_US
dc.typeTexten_US
dc.typeImageen_US
dc.typeAudiovisualen_US
dc.description.versionFor reviewen_US
tud.unitTUDa


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Creative Commons Attribution-NonCommercial 4.0
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