Inheritance of silent rDNA chromatin is mediated by PARP1 via noncoding RNA

Mol Cell. 2012 Mar 30;45(6):790-800. doi: 10.1016/j.molcel.2012.01.024. Epub 2012 Mar 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Diphosphate / metabolism
  • Animals
  • Chromatin / genetics*
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Replication
  • DNA, Ribosomal / metabolism*
  • Gene Silencing
  • Heterochromatin
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases / genetics
  • Poly(ADP-ribose) Polymerases / metabolism*
  • RNA, Ribosomal / metabolism
  • RNA, Untranslated / metabolism*

Substances

  • BAZ2A protein, human
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA, Ribosomal
  • Heterochromatin
  • RNA, Ribosomal
  • RNA, Untranslated
  • Adenosine Diphosphate
  • PARP1 protein, human
  • Parp1 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases