The chromatin remodeling complex NoRC controls replication timing of rRNA genes

被引:91
作者
Li, JW
Santoro, R
Koberna, K
Grummt, I
机构
[1] DKFZ, German Canc Res Ctr, Div Mol Biol Cell 2, D-69120 Heidelberg, Germany
[2] Charles Univ Prague, Acad Sci Czech Republ, Inst Expt Med, Prague, Czech Republic
[3] Charles Univ Prague, Fac Med 1, Inst Cellular Biol & Pathol, Prague, Czech Republic
关键词
DNA methylation; histone modification; NoRC; replication; RNA polymerase I;
D O I
10.1038/sj.emboj.7600492
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
The ATP- dependent chromatin remodeling complex NoRC silences a fraction of mammalian ribosomal RNA genes ( rDNA) by establishing heterochromatic structures at the rDNA promoter. Here we show that NoRC also plays a role in replication timing of rDNA. rDNA is replicated in a biphasic manner, active genes ( similar to60%) replicating early and silent ones ( similar to40%) replicating late in S- phase. The chromatin structure that marks active and silent rDNA repeats is propagated during cell division. To examine the function of NoRC in epigenetic inheritance and replication timing, we have monitored the chromatin structure, transcriptional activity and replication timing of rDNA in a cell line that moderately overexpresses NoRC. NoRC is exclusively associated with late- replicating rDNA arrays. Overexpression of NoRC silences rDNA transcription, reduces the size and number of nucleoli, impairs cell proliferation and resets replication timing from early to late. The results demonstrate that NoRC is an important determinant of replication timing and epigenetic marks are heritably maintained through DNA replication.
引用
收藏
页码:120 / 127
页数:8
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