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Dynamic association of H3K36me3 with pericentromeric heterochromatin regulates its replication time

dc.contributor.author Cardoso, M. Cristina
dc.contributor.author Rapp, Alexander
dc.contributor.author Arroyo, Maria
dc.contributor.author Zhang, Hui
dc.contributor.author Kolobynina, Ksenia G.
dc.contributor.author Pradhan, Sunil Kumar
dc.date.accessioned 2025-06-13T11:18:16Z
dc.date.available 2025-03-03T09:39:32Z
dc.date.created 2025
dc.date.issued 2025-06-13
dc.description The flexibility of the spatio-temporal genome replication program during development and disease highlights the regulatory role of plastic epigenetic mechanisms over genetic determinants. Histone post-translational modifications are broadly implicated in replication timing control, yet the specific mechanisms through which individual histone marks influence replication dynamics, particularly in heterochromatin, remain unclear. Here, we demonstrate that H3K36me3 dynamically enriches at pericentromeric heterochromatin, composed of major satellite DNA repeats, prior to replication during mid S phase in mouse embryonic stem cells. By knocking down lysine 36-specific methyltransferases or by targeting the H3K36M oncohistone to pericentromeric heterochromatin, we reduce global or local H3K36me3 levels, respectively, revealing its essential role in preserving the replication timing of constitutive heterochromatin. Loss of H3K36me3 accompanies increased RNA polymerase II serine-5 phosphorylation and lowered major satellite RNA levels, indicating transcriptional dysregulation. Notably, we identify a strand-specific contribution of major satellite forward transcripts in regulating the replication timing of constitutive heterochromatin and maintaining chromatin stability, highlighting the importance of non-coding RNAs as critical regulators of replication timing. en
dc.identifier.uri https://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/4482.3
dc.identifier.uri https://doi.org/10.48328/tudatalib-1681.3
dc.language.iso en de_DE
dc.rights.licenseCC-BY-NC-4.0 (https://creativecommons.org/licenses/by-nc/4.0)
dc.subject H3K36me3 de_DE
dc.subject pericentromeric heterochromatin de_DE
dc.subject H3.1 K36M de_DE
dc.subject MaSat RNA de_DE
dc.subject replication timing de_DE
dc.subject.classification 2.11-03
dc.subject.ddc 570
dc.title Dynamic association of H3K36me3 with pericentromeric heterochromatin regulates its replication time en
dc.type Dataset de_DE
dc.type Text de_DE
dc.type Image de_DE
dc.type Other de_DE
dcterms.accessRights openAccess
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tuda.unit TUDa

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VersionDateSummary
2025-08-21 11:48:31
Dynamic association of H3K36me3 with pericentromeric heterochromatin regulates its replication time
3*
2025-06-13 11:18:01
Dynamic association of H3K36me3 with pericentromeric heterochromatin regulates its replication time
2025-06-12 15:52:15
Dynamic association of H3K36me3 with pericentromeric heterochromatin promotes its transcription to regulate replication timing through major satellite RNA
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