title: Asymmetrically modified nucleosomes.
abstract: Mononucleosomes, the basic building blocks of chromatin, contain two copies of each core histone. The associated posttranslational modifications regulate essential chromatin-dependent processes, yet whether each histone copy is identically modified in vivo is unclear. We demonstrate that nucleosomes in embryonic stem cells, fibroblasts, and cancer cells exist in both symmetrically and asymmetrically modified populations for histone H3 lysine 27 di/trimethylation (H3K27me2/3) and H4K20me1. Further, we obtained direct physical evidence for bivalent nucleosomes carrying H3K4me3 or H3K36me3 along with H3K27me3, albeit on opposite H3 tails. Bivalency at target genes was resolved upon differentiation of ES cells. Polycomb repressive complex 2-mediated methylation of H3K27 was inhibited when nucleosomes contain symmetrically, but not asymmetrically, placed H3K4me3 or H3K36me3. These findings uncover a potential mechanism for the incorporation of bivalent features into nucleosomes and demonstrate how asymmetry might set the stage to diversify functional nucleosome states.
authors.affiliation: Howard Hughes Medical Institute, New York University School of Medicine, Department of Biochemistry, New York, NY 10016, USA.
authors.forename: Philipp
authors.initials: P
authors.lastname: Voigt
authors.forename: Gary
authors.initials: G
authors.lastname: LeRoy
authors.forename: William J
authors.initials: WJ
authors.lastname: Drury
authors.forename: Barry M
authors.initials: BM
authors.lastname: Zee
authors.forename: Jinsook
authors.initials: J
authors.lastname: Son
authors.forename: David B
authors.initials: DB
authors.lastname: Beck
authors.forename: Nicolas L
authors.initials: NL
authors.lastname: Young
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
authors.forename: Danny
authors.initials: D
authors.lastname: Reinberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006367:HeLa Cells; D042421:Histone Code; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism*; D063146:Polycomb-Group Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011499:Protein Processing, Post-Translational
chemical_list: D006657:Histones; D009707:Nucleosomes; D063146:Polycomb-Group Proteins