Oleksiewicz, UrszulaGladych, MartaRaman, Ayush T.Heyn, HolgerMereu, ElisabettaChlebanowska, PaulaAndrzejewska, AnastazjaSozanska, BarbaraSamant, NehaFak, KatarzynaAuguscik, PaulinaKosinski, MarcinWroblewska, Joanna P.Tomczak, KatarzynaKulcenty, KatarzynaPloski, RafalBiecek, PrzemyslawEsteller, ManelShah, Parantu K.Rai, KunalWiznerowicz, Maciej2018-08-292018-08-292017-12-012213-6711https://hdl.handle.net/2445/124165Reprogramming 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 Kruppel-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.16 p.application/pdfengcc-by (c) Oleksiewicz, Urszula et al., 2017http://creativecommons.org/licenses/by/3.0/esCèl·lules mareEpigenèticaADNStem cellsEpigeneticsDNAinfo:eu-repo/semantics/article6768782018-08-29info:eu-repo/semantics/openAccess29198826