Oleksiewicz, UrszulaGładych, MartaRaman, Ayush T.Heyn, HolgerMereu, ElisabettaChlebanowska, PaulaAndrzejewska, AnastazjaSozańska, BarbaraSamant, NehaFąk, KatarzynaAuguścik, PaulinaKosiński, MarcinWróblewska, Joanna P.Tomczak, KatarzynaKulcenty, KatarzynaPłoski, RafałBiecek, PrzemysławEsteller, ManelShah, Parantu K.Rai, KunalWiznerowicz, Maciej2018-07-242018-07-242017Oleksiewicz 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.2017.10.0312045-2322http://hdl.handle.net/10230/35244Reprogramming 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.application/pdfeng© 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/)info:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.stemcr.2017.10.031Krab-znf repressorsTrim28DifferentiationEpigeneticsInduced pluripotent stem cellsReprogramminginfo:eu-repo/semantics/openAccess