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Dynamic association of H3K36me3 with pericentromeric heterochromatin promotes its transcription to regulate replication timing

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 2025-06-13T08:37:19Z
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 have been 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 the dynamic enrichment of H3K36me3 at pericentromeric heterochromatin (PCHs) consisting of major satellite (MajSat) repeats preceding replication during the S II sub-phase in mouse embryonic stem cells. Through the knock down of lysine 36 specific methyltransferases or targeted introduction of oncohistone to PCHs, we reduced both global or local H3K36me3 levels, respectively, revealing its essential role in preserving the replication timing of constitutive heterochromatin. Loss of H3K36me3 was accompanied by increased RNA polymerase II serine-5 phosphorylation but reduced MajSat RNA levels, indicating transcriptional dysregulation. Notably, we identify a strand-specific contribution of MajSat forward transcripts in regulating the replication timing of PCHs and maintaining chromatin stability, highlighting the importance of non-coding RNAs as critical regulators of replication timing. de_DE
dc.identifier.uri https://tudatalib.ulb.tu-darmstadt.de/handle/tudatalib/4482.2
dc.identifier.uri https://doi.org/10.48328/tudatalib-1681.2
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 promotes its transcription to regulate replication timing de_DE
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.agreements true
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
2025-06-13 11:18:01
Dynamic association of H3K36me3 with pericentromeric heterochromatin regulates its replication time
2*
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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