Inheritance of Silent rDNA Chromatin Is Mediated by PARP1 via Noncoding RNA
Inheritance of Silent rDNA Chromatin Is Mediated by PARP1 via Noncoding RNA
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DOI：
10.1016/j.molcel.2012.01.024
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发表时间：
2012-03-30
期刊：
影响因子：
16
通讯作者：
Santoro, Raffaella
中科院分区：
文献类型：
--
作者：
Guetg, Claudio;Scheifele, Fabian;Santoro, Raffaella
特定染色质状态的忠实传播需要在每次细胞分裂后重建表观遗传标记。 DNA 复制过程中受到破坏后，最初的表观遗传特征是如何遗传的仍然知之甚少。在这里，我们证明聚（ADP-核糖）-聚合酶-1（PARP1/ARTD1）与细胞分裂过程中沉默 rDNA 染色质的维持有关。我们证明 PARP1 通过非编码 pRNA 与 NoRC 复合物的一个亚基 TIP5 结合，并在 S 期中后期复制后与沉默的 rRNA 基因结合。 PARP1 抑制 rRNA 转录并参与沉默 rDNA 染色质的形成。沉默的 rDNA 染色质是 ADP-核糖基化的特异性底物，PARP1 的酶活性对于建立 rDNA 沉默是必需的。这些数据揭示了 PARP1 和 ADP 核糖基化的功能，该功能有助于沉默染色质结构的遗传，从而揭示表观遗传标记在每个细胞周期中如何传递。
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.