title: The murine polycomb group protein Eed is required for global histone H3 lysine-27 methylation.
abstract: PcG proteins mediate heritable transcriptional silencing by generating and recognizing covalent histone modifications. One conserved PcG complex, PRC2, is composed of several proteins including the histone methyltransferase (HMTase) Ezh2, the WD-repeat protein Eed, and the Zn-finger protein Suz12. Ezh2 methylates histone H3 on lysine 27 (H3K27), which serves as an epigenetic mark mediating silencing. H3K27 can be mono-, di-, or trimethylated (1mH3K27, 2mH3K27, and 3mH3K27, respectively). Hence, either PRC2 must be regulated so as to add one methyl group to certain nucleosomes but two or three to others, or distinct complexes must be responsible for 1m-, 2m-, and 3mH3K27. Consistent with the latter possibility, 2mH3K27 and 3mH3K27, but not 1mH3K27, are absent in Suz12-/- embryos, which lack both Suz12 and Ezh2 protein. Mammalian proteins required for 1mH3K27 have not been identified. Here, we demonstrate that unlike Suz12 and Ezh2, Eed is required not only for 2m- and 3mH3K27 but also global 1mH3K27. These results provide a functionally important distinction between PRC2 complex components and implicate Eed in PRC2-independent histone methylation.
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Call Box #7264, Chapel Hill, North Carolina 27599, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Montgomery
authors.forename: Della
authors.initials: D
authors.lastname: Yee
authors.forename: Andrew
authors.initials: A
authors.lastname: Chen
authors.forename: Sundeep
authors.initials: S
authors.lastname: Kalantry
authors.forename: Stormy J
authors.initials: SJ
authors.lastname: Chamberlain
authors.forename: Arie P
authors.initials: AP
authors.lastname: Otte
authors.forename: Terry
authors.initials: T
authors.lastname: Magnuson
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D003001:Cloning, Molecular; D004622:Embryo, Mammalian / Q000166:cytology; D044127:Epigenesis, Genetic / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D020868:Gene Silencing / Q000502:physiology*; D005822:Genetic Vectors; D006657:Histones / Q000378:metabolism*; D008239:Lysine; D008745:Methylation; D051379:Mice; D063151:Polycomb Repressive Complex 2; D012097:Repressor Proteins / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000378:metabolism
chemical_list: C107275:Eed protein, mouse; D006657:Histones; D012097:Repressor Proteins; D063151:Polycomb Repressive Complex 2; D008239:Lysine