title: Inheritance of silent rDNA chromatin is mediated by PARP1 via noncoding RNA.
abstract: Faithful propagation of specific chromatin states requires re-establishment of epigenetic marks after every cell division. How the original epigenetic signature is inherited after disruption during DNA replication is still poorly understood. Here, we show that the poly(ADP-ribose)-polymerase-1 (PARP1/ARTD1) is implicated in the maintenance of silent rDNA chromatin during cell division. We demonstrate that PARP1 associates with TIP5, a subunit of the NoRC complex, via the noncoding pRNA and binds to silent rRNA genes after their replication in mid-late S phase. PARP1 represses rRNA transcription and is implicated in the formation of silent rDNA chromatin. Silent rDNA chromatin is a specific substrate for ADP-ribosylation and the enzymatic activity of PARP1 is necessary to establish rDNA silencing. The data unravel a function of PARP1 and ADP-ribosylation that serves to allow for the inheritance of silent chromatin structures, shedding light on how epigenetic marks are transmitted during each cell cycle.
authors.affiliation: Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Claudio
authors.initials: C
authors.lastname: Guetg
authors.forename: Fabian
authors.initials: F
authors.lastname: Scheifele
authors.forename: Florian
authors.initials: F
authors.lastname: Rosenthal
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
authors.forename: Raffaella
authors.initials: R
authors.lastname: Santoro
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004275:DNA, Ribosomal / Q000378:metabolism*; D020868:Gene Silencing; D006570:Heterochromatin; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000378:metabolism; D022661:RNA, Untranslated / Q000378:metabolism*; D000092468:Bromodomain Containing Proteins
chemical_list: D000244:Adenosine Diphosphate; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004275:DNA, Ribosomal; D006570:Heterochromatin; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D012335:RNA, Ribosomal; D022661:RNA, Untranslated; C436708:BAZ2A protein, human; D000092468:Bromodomain Containing Proteins; C499320:PARP1 protein, human; C499321:Parp1 protein, mouse