TRIM28 and Interacting KRAB-ZNFs control self-renewal of human pluripotent stem cells through epigenetic repression of pro-differentiation genes
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- dc.contributor.author Oleksiewicz, Urszulaca
- dc.contributor.author Gładych, Martaca
- dc.contributor.author Raman, Ayush T.ca
- dc.contributor.author Heyn, Holgerca
- dc.contributor.author Mereu, Elisabettaca
- dc.contributor.author Chlebanowska, Paulaca
- dc.contributor.author Andrzejewska, Anastazjaca
- dc.contributor.author Sozańska, Barbaraca
- dc.contributor.author Samant, Nehaca
- dc.contributor.author Fąk, Katarzynaca
- dc.contributor.author Auguścik, Paulinaca
- dc.contributor.author Kosiński, Marcinca
- dc.contributor.author Wróblewska, Joanna P.ca
- dc.contributor.author Tomczak, Katarzynaca
- dc.contributor.author Kulcenty, Katarzynaca
- dc.contributor.author Płoski, Rafałca
- dc.contributor.author Biecek, Przemysławca
- dc.contributor.author Esteller, Manelca
- dc.contributor.author Shah, Parantu K.ca
- dc.contributor.author Rai, Kunalca
- dc.contributor.author Wiznerowicz, Maciejca
- dc.date.accessioned 2018-07-24T07:55:47Z
- dc.date.available 2018-07-24T07:55:47Z
- dc.date.issued 2017
- dc.description.abstract Reprogramming to induced pluripotent stem cells (iPSCs) and differentiation of pluripotent stem cells (PSCs) are regulated by epigenetic machinery. Tripartite motif protein 28 (TRIM28), a universal mediator of Krüppel-associated box domain zinc fingers (KRAB-ZNFs), is known to regulate both processes; however, the exact mechanism and identity of participating KRAB-ZNF genes remain unknown. Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming. Using several expression datasets, we identified KRAB-ZNFs (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency. Moreover, we identified target genes repressed by these KRAB-ZNFs. Mechanistically, we demonstrated that these KRAB-ZNFs directly alter gene expression of important developmental genes by modulating H3K9me3 and DNA methylation of their promoters. In summary, TRIM28 employs KRAB-ZNFs to evoke epigenetic silencing of its target differentiation genes via H3K9me3 and DNA methylation.
- dc.format.mimetype application/pdf
- dc.identifier.citation Oleksiewicz U, Gładych M, Raman AT, Heyn H, Mereu E, Chlebanowska P et al. TRIM28 and Interacting KRAB-ZNFs Control Self-Renewal of Human Pluripotent Stem Cells through Epigenetic Repression of Pro-differentiation Genes. Stem Cell Reports. 2017 Dec 12;9(6):2065-80. DOI: 10.1016/j.stemcr.2017.10.031
- dc.identifier.doi http://dx.doi.org/10.1016/j.stemcr.2017.10.031
- dc.identifier.issn 2045-2322
- dc.identifier.uri http://hdl.handle.net/10230/35244
- dc.language.iso eng
- dc.publisher Elsevierca
- dc.relation.ispartof Stem Cell Reports. 2017 Dec 12;9(6):2065-80
- dc.rights © 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.keyword Krab-znf repressors
- dc.subject.keyword Trim28
- dc.subject.keyword Differentiation
- dc.subject.keyword Epigenetics
- dc.subject.keyword Induced pluripotent stem cells
- dc.subject.keyword Reprogramming
- dc.title TRIM28 and Interacting KRAB-ZNFs control self-renewal of human pluripotent stem cells through epigenetic repression of pro-differentiation genesca
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion