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Chromatin targeting signals nucleosome positioning mechanism and non-coding RNA mediated regulation of the chromatin remodeling complex NoRC
- Source :
- PLoS Genetics, Vol 10, Iss 3, p e1004157 (2014), PLoS Genetics
- Publication Year :
- 2014
- Publisher :
- Universität Regensburg, 2014.
-
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.<br />Author Summary Tumour cells overexpress ribosomal RNA (rRNA), which is required for ribosome assembly and cell growth. rRNA gene repression is mediated by the chromatin remodeling complex (NoRC) and a non-coding RNA that binds to this enzyme. This study addresses the mechanism of nucleosome positioning by NoRC and the functional role of the non-coding RNA, which is termed pRNA because it corresponds to the promoter sequence. NoRC recognises the promoter nucleosome in a chromatin array with high affinity and uses a release mechanism to position the nucleosome over the transcription initiation site. The pRNA binds specifically to NoRC and inhibits its ATPase activity. We suggest that the RNA retains NoRC at the gene promoter after remodeling, linking its chromatin modification and scaffolding activity to inactive rDNA copies.
- Subjects :
- RNA, Untranslated
lcsh:QH426-470
Biophysics
Gene Expression
Biochemistry
Epigenesis, Genetic
Histones
Mice
Nucleic Acids
Genetics
Animals
570 Biowissenschaften, Biologie
Biomacromolecule-Ligand Interactions
Promoter Regions, Genetic
Biology
Adenosine Triphosphatases
Nuclear Proteins
Proteins
Acetylation
Chromatin Assembly and Disassembly
Chromatin
Nucleosomes
Enzymes
lcsh:Genetics
RNA, Ribosomal
Multiprotein Complexes
ddc:570
Gene Function
Research Article
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- PLoS Genetics, Vol 10, Iss 3, p e1004157 (2014), PLoS Genetics
- Accession number :
- edsair.doi.dedup.....bd76a968aedec9c1875accd96a49f785
- Full Text :
- https://doi.org/10.5283/epub.30013