title: Product binding enforces the genomic specificity of a yeast polycomb repressive complex.
abstract: We characterize the Polycomb system that assembles repressive subtelomeric domains of H3K27 methylation (H3K27me) in the yeast Cryptococcus neoformans. Purification of this PRC2-like protein complex reveals orthologs of animal PRC2 components as well as a chromodomain-containing subunit, Ccc1, which recognizes H3K27me. Whereas removal of either the EZH or EED ortholog eliminates H3K27me, disruption of mark recognition by Ccc1 causes H3K27me to redistribute. Strikingly, the resulting pattern of H3K27me coincides with domains of heterochromatin marked by H3K9me. Indeed, additional removal of the C. neoformans H3K9 methyltransferase Clr4 results in loss of both H3K9me and the redistributed H3K27me marks. These findings indicate that the anchoring of a chromatin-modifying complex to its product suppresses its attraction to a different chromatin type, explaining how enzymes that act on histones, which often harbor product recognition modules, may deposit distinct chromatin domains despite sharing a highly abundant and largely identical substrate-the nucleosome.
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Dumesic
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Homer
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Moresco
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Pack
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Erin K
authors.initials: EK
authors.lastname: Shanle
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Coyle
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Strahl
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94158, USA.
authors.forename: Danica G
authors.initials: DG
authors.lastname: Fujimori
authors.affiliation: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: hitenmadhani@gmail.com.
authors.forename: Hiten D
authors.initials: HD
authors.lastname: Madhani
mesh_terms: D000595:Amino Acid Sequence; D002503:Centromere / Q000378:metabolism; D003455:Cryptococcus neoformans / Q000235:genetics / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism*; D006570:Heterochromatin / Q000378:metabolism; D042421:Histone Code; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D008969:Molecular Sequence Data; D063146:Polycomb-Group Proteins / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D005656:Fungal Proteins; D006570:Heterochromatin; D063146:Polycomb-Group Proteins; D011495:Histone-Lysine N-Methyltransferase