The NoRC complex mediates the heterochromatin formation and stability of silent rRNA genes and centromeric repeats

被引：147

作者：

Guetg, Claudio ^{[1
,2
,3
]}

Lienemann, Philipp ^{[2
]}

Sirri, Valentina ^{[4
,5
]}

Grummt, Ingrid ^{[6
]}

Hernandez-Verdun, Daniele ^{[4
,5
]}

Hottiger, Michael O. ^{[1
]}

Fussenegger, Martin ^{[2
]}

Santoro, Raffaella ^{[1
,2
]}

机构：

[1] Univ Zurich, Inst Vet Biochem & Mol Biol, CH-8057 Zurich, Switzerland

[2] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, Basel, Switzerland

[3] Univ Zurich, Life Sci Zurich Grad Sch, Mol Life Sci Program, CH-8057 Zurich, Switzerland

[4] Univ Paris 07, Paris, France

[5] Inst Jacques Monod, CNRS, UMR 7592, F-75251 Paris, France

[6] INF 581, DKFZ ZMBH Alliance, German Canc Res Ctr, Div Mol Biol Cell 2, Heidelberg, Germany

来源：

EMBO JOURNAL | 2010年 / 29卷 / 13期

基金：

瑞士国家科学基金会;

关键词：

cell proliferation; genomic stability; heterochromatin; NoRC; rDNA silencing; POLYMERASE-I TRANSCRIPTION; MUS-MUSCULUS; METHYLATION STATES; DNA METHYLATION; S-PHASE; CHROMATIN; MOUSE; NUCLEOLUS; PROTEIN; ORGANIZATION;

D O I：

10.1038/emboj.2010.17

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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

引用

页码：2135 / 2146

页数：12

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