title: The polycomb protein Ezh2 impacts on induced pluripotent stem cell generation.
abstract: Reprogramming of somatic cells toward pluripotency involves extensive chromatin reorganization and changes in gene expression. Polycomb group (PcG) proteins are key regulators of chromatin structure, cell identity, and development. In this study, we investigated the impact of Ezh2, a core subunit of Polycomb repressive complex 2 (PRC2), on the generation of induced pluripotent stem (iPS) cells. We found that Ezh2 expression is induced during iPS cell generation and iPS cells contain high levels of Ezh2 mRNA and protein. Importantly, shRNA knockdown of Ezh2 during reprogramming severely impairs iPS cell generation. Mechanistically, Ezh2 acts during reprogramming at least in part through repressing the Ink4a/Arf locus, which represents a major roadblock for iPS cell generation. Interestingly, knockdown of Ezh2 in established pluripotent cells leaves pluripotency and self-renewal of embryonic stem cells and iPS cells unaffected. Altogether, our results demonstrate that Ezh2 is critical for efficient iPS cell generation, whereas it is dispensable for maintaining the reprogrammed iPS cell state.
authors: 1 Department of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University Medical School , Aachen, Germany .
authors: Xiaolei
authors: X
authors: Ding
authors: Xiaoying
authors: X
authors: Wang
authors: Stephanie
authors: S
authors: Sontag
authors: Jie
authors: J
authors: Qin
authors: Paul
authors: P
authors: Wanek
authors: Qiong
authors: Q
authors: Lin
authors: Martin
authors: M
authors: Zenke
mesh_terms: D000818:Animals; D002460:Cell Line; D065150:Cellular Reprogramming; D000071221:Enhancer of Zeste Homolog 2 Protein; D056426:Genetic Loci; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D063151:Polycomb Repressive Complex 2 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071221:Enhancer of Zeste Homolog 2 Protein; C498410:Ezh2 protein, mouse; D063151:Polycomb Repressive Complex 2