The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats
The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats
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DOI：
10.1038/emboj.2010.17
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发表时间：
2010-07-07
期刊：
影响因子：
11.4
通讯作者：
Santoro, Raffaella
中科院分区：
文献类型：
--
作者：
Guetg, Claudio;Lienemann, Philipp;Santoro, Raffaella
维持特定的异染色质结构域对于基因组的稳定性至关重要。在真核细胞中，部分串联重复的核糖体RNA(RRNA)基因被组织在异染色质结构中。RDNA沉默的主要决定因素是核仁重塑复合体NORC，它由TIP5(TTF-1相互作用蛋白-5)和ATPase Snf2H组成。在这里，我们发现TIP5不仅介导了rDNA沉默的建立，而且还参与了核仁周围异染色质的形成，该异染色质包括中心重复序列和中心重复序列。我们的数据表明，TIP5介导的异染色质对于沉默的rRNA基因和主要和次要的卫星重复序列的稳定是必不可少的。此外，TIP5的缺失会削弱rDNA沉默，上调rDNA转录水平，并诱导细胞转化。这些发现指出了TIP5在保护基因组稳定性方面的作用，并表明它可以在细胞转化过程中发挥作用。EMBO期刊(2010)29,2135-2146。DOI：10.1038/Intemj.2010.17；2010年2月18日在线发布
Maintenance of specific heterochromatic domains is crucial for genome stability. In eukaryotic cells, a fraction of the tandem-repeated ribosomal RNA (rRNA) genes is organized in the heterochromatic structures. The principal determinant of rDNA silencing is the nucleolar remodelling complex, NoRC, that consists of TIP5 (TTF-1-interacting protein-5) and the ATPase SNF2h. Here we showed that TIP5 not only mediates the establishment of rDNA silencing but also the formation of perinucleolar heterochromatin that contains centric and pericentric repeats. Our data indicated that the TIP5-mediated heterochromatin is indispensable for stability of silent rRNA genes and of major and minor satellite repeats. Moreover, depletion of TIP5 impairs rDNA silencing, upregulates rDNA transcription levels and induces cell transformation. These findings point to a role of TIP5 in protecting genome stability and suggest that it can play a role in the cellular transformation process. The EMBO Journal (2010) 29, 2135-2146. doi:10.1038/emboj.2010.17; Published online 18 February 2010