Inheritance of Silent rDNA Chromatin Is Mediated by PARP1 via Noncoding RNA

被引:126
作者
Guetg, Claudio [1 ,2 ]
Scheifele, Fabian [1 ]
Rosenthal, Florian [1 ,2 ]
Hottiger, Michael O. [1 ]
Santoro, Raffaella [1 ]
机构
[1] Univ Zurich, Inst Vet Biochem & Mol Biol, CH-8057 Zurich, Switzerland
[2] Univ Zurich, Life Sci Zurich Grad Sch, Mol Life Sci Program, CH-8057 Zurich, Switzerland
基金
瑞士国家科学基金会;
关键词
REMODELING COMPLEX NORC; RIBOSYLATED NUCLEAR PROTEINS; RIBOSOMAL GENE-TRANSCRIPTION; DNA-POLYMERASE-ALPHA; POLY(ADP-RIBOSE) POLYMERASE; HETEROCHROMATIN FORMATION; HISTONE MODIFICATION; REPLICATION FORKS; ADP-RIBOSYLATION; TUMOR-CELLS;
D O I
10.1016/j.molcel.2012.01.024
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:790 / 800
页数:11
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