2026-05-22T17:21:21Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/100072024-11-29T16:48:22Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
Scarola, Michele
author
Comisso, Elisa
author
Pascolo, Rhena
author
Chiaradia, Riccardo
author
Marion, RM
author
Schneider, Claudio
author
Blasco, MA
author
Schoeftner, Stefan
author
Benetti, Roberta
funder
Italian Association for Cancer Research
funder
Fondazione Umberto Veronesi
funder
Ministero dell Istruzione, dell Universita e della Ricerca (Italia)
2020-05-08T17:30:56Z
2020-05-08T17:30:56Z
2015-07-09
Nat Commun. 2015;6:763
10.1038/ncomms8631
2041-1723
2041-1723
Nature communications
26158551
http://hdl.handle.net/20.500.12105/10007
Pseudogene-derived, long non-coding RNAs (lncRNAs) act as epigenetic regulators of gene expression. Here we present a panel of new mouse Oct4 pseudogenes and demonstrate that the X-linked Oct4 pseudogene Oct4P4 critically impacts mouse embryonic stem cells (mESCs) self-renewal. Sense Oct4P4 transcription produces a spliced, nuclear-restricted lncRNA that is efficiently upregulated during mESC differentiation. Oct4P4 lncRNA forms a complex with the SUV39H1 HMTase to direct the imposition of H3K9me3 and HP1α to the promoter of the ancestral Oct4 gene, located on chromosome 17, leading to gene silencing and reduced mESC self-renewal. Targeting Oct4P4 expression in primary mouse embryonic fibroblasts causes the re-acquisition of self-renewing features of mESC. We demonstrate that Oct4P4 lncRNA plays an important role in inducing and maintaining silencing of the ancestral Oct4 gene in differentiating mESCs. Our data introduces a sense pseudogene-lncRNA-based mechanism of epigenetic gene regulation that controls the cross-talk between pseudogenes and their ancestral genes.
eng
Epigenetic silencing of Oct4 by a complex containing SUV39H1 and Oct4 pseudogene lncRNA
journal article
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