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Título:	TRIM28 and Interacting KRAB-ZNFs Control Self-Renewal of Human Pluripotent Stem Cells through Epigenetic Repression of Pro-differentiation Genes
Autor/a:	Oleksiewicz, Urszula; Gladych, Marta; Raman, Ayush T.; Heyn, Holger; Mereu, Elisabetta; Chlebanowska, Paula; Andrzejewska, Anastazja; Sozanska, Barbara; Samant, Neha; Fak, Katarzyna; Auguscik, Paulina; Kosinski, Marcin; Wroblewska, Joanna P.; Tomczak, Katarzyna; Kulcenty, Katarzyna; Ploski, Rafal; Biecek, Przemyslaw; Esteller, Manel; Shah, Parantu K.; Rai, Kunal; Wiznerowicz, Maciej
Otros autores:	Universitat de Barcelona
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 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.
Materia(s):	-Cèl·lules mare -Epigenètica -ADN -Stem cells -Epigenetics -DNA
Derechos:	cc-by (c) Oleksiewicz, Urszula et al., 2017 http://creativecommons.org/licenses/by/3.0/es
Tipo de documento:	Artículo Artículo - Versión publicada
Editor:	Elsevier
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