title: The chromatin remodeling complex NoRC controls replication timing of rRNA genes.
abstract: 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 ( approximately 60%) replicating early and silent ones ( approximately 40%) 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.
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Junwei
authors.initials: J
authors.lastname: Li
authors.forename: Raffaella
authors.initials: R
authors.lastname: Santoro
authors.forename: Karel
authors.initials: K
authors.lastname: Koberna
authors.forename: Ingrid
authors.initials: I
authors.lastname: Grummt
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D048430:Cell Shape; D002843:Chromatin / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D041681:NIH 3T3 Cells; D009690:Nucleic Acid Conformation; D011401:Promoter Regions, Genetic; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000235:genetics*; D000092468:Bromodomain Containing Proteins
chemical_list: D000255:Adenosine Triphosphate; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004275:DNA, Ribosomal; D046911:Macromolecular Substances; D012322:RNA Precursors; D012335:RNA, Ribosomal; C436708:BAZ2A protein, human; D000092468:Bromodomain Containing Proteins; C499051:Baz2a protein, mouse