title: Polycomb repressive complex 2 is dispensable for maintenance of embryonic stem cell pluripotency.
abstract: Polycomb repressive complex 2 (PRC2) methylates histone H3 tails at lysine 27 and is essential for embryonic development. The three core components of PRC2, Eed, Ezh2, and Suz12, are also highly expressed in embryonic stem (ES) cells, where they are postulated to repress developmental regulators and thereby prevent differentiation to maintain the pluripotent state. We performed gene expression and chimera analyses on low- and high-passage Eed(null) ES cells to determine whether PRC2 is required for the maintenance of pluripotency. We report here that although developmental regulators are overexpressed in Eed(null) ES cells, both low- and high-passage cells are functionally pluripotent. We hypothesize that they are pluripotent because they maintain expression of critical pluripotency factors. Given that EED is required for stability of EZH2, the catalytic subunit of the complex, these data suggest that PRC2 is not necessary for the maintenance of the pluripotent state in ES cells. We propose a positive-only model of embryonic stem cell maintenance, where positive regulation of pluripotency factors is sufficient to mediate stem cell pluripotency. Disclosure of potential conflicts of interest is found at the end of this article.
authors.affiliation: Department of Genetics and Carolina Center for Genome Sciences, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors.forename: Stormy J
authors.initials: SJ
authors.lastname: Chamberlain
authors.forename: Della
authors.initials: D
authors.lastname: Yee
authors.forename: Terry
authors.initials: T
authors.lastname: Magnuson
mesh_terms: D000818:Animals; D002678:Chimera / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology*; D007150:Immunohistochemistry; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000502:physiology*; D063151:Polycomb Repressive Complex 2; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C107275:Eed protein, mouse; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse; D010089:Oxidoreductases, N-Demethylating; D063151:Polycomb Repressive Complex 2; D008239:Lysine