title: Chromatin targeting signals, nucleosome positioning mechanism and non-coding RNA-mediated regulation of the chromatin remodeling complex NoRC.
abstract: Active and repressed ribosomal RNA (rRNA) genes are characterised by specific epigenetic marks and differentially positioned nucleosomes at their promoters. Repression of the rRNA genes requires a non-coding RNA (pRNA) and the presence of the nucleolar remodeling complex (NoRC). ATP-dependent chromatin remodeling enzymes are essential regulators of DNA-dependent processes, and this regulation occurs via the modulation of DNA accessibility in chromatin. We have studied the targeting of NoRC to the rRNA gene promoter; its mechanism of nucleosome positioning, in which a nucleosome is placed over the transcription initiation site; and the functional role of the pRNA. We demonstrate that NoRC is capable of recognising and binding to the nucleosomal rRNA gene promoter on its own and binds with higher affinity the nucleosomes positioned at non-repressive positions. NoRC recognises the promoter nucleosome within a chromatin array and positions the nucleosomes, as observed in vivo. NoRC uses the release mechanism of positioning, which is characterised by a reduced affinity for the remodeled substrate. The pRNA specifically binds to NoRC and regulates the enzyme by switching off its ATPase activity. Given the known role of pRNA in tethering NoRC to the rDNA, we propose that pRNA is a key factor that links the chromatin modification activity and scaffolding function of NoRC.
authors.affiliation: Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Manelyte
authors.affiliation: Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Strohner
authors.affiliation: Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gross
authors.affiliation: Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Längst
mesh_terms: D000107:Acetylation; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D002843:Chromatin / Q000235:genetics; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D044127:Epigenesis, Genetic; D006657:Histones / Q000235:genetics; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D009707:Nucleosomes / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012335:RNA, Ribosomal / Q000235:genetics*; D022661:RNA, Untranslated / Q000235:genetics*
chemical_list: D002843:Chromatin; D006657:Histones; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D009707:Nucleosomes; D012335:RNA, Ribosomal; D022661:RNA, Untranslated; D000251:Adenosine Triphosphatases