title: lncRNA-Induced Nucleosome Repositioning Reinforces Transcriptional Repression of rRNA Genes upon Hypotonic Stress.
abstract: The activity of rRNA genes (rDNA) is regulated by pathways that target the transcription machinery or alter the epigenetic state of rDNA. Previous work has established that downregulation of rRNA synthesis in quiescent cells is accompanied by upregulation of PAPAS, a long noncoding RNA (lncRNA) that recruits the histone methyltransferase Suv4-20h2 to rDNA, thus triggering trimethylation of H4K20 (H4K20me3) and chromatin compaction. Here, we show that upregulation of PAPAS in response to hypoosmotic stress does not increase H4K20me3 because of Nedd4-dependent ubiquitinylation and proteasomal degradation of Suv4-20h2. Loss of Suv4-20h2 enables PAPAS to interact with CHD4, a subunit of the chromatin remodeling complex NuRD, which shifts the promoter-bound nucleosome into the transcriptional "off" position. Thus, PAPAS exerts a "stress-tailored" dual function in rDNA silencing, facilitating either Suv4-20h2-dependent chromatin compaction or NuRD-dependent changes in nucleosome positioning.
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Zhongliang
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Marcel Andre
authors.initials: MA
authors.lastname: Dammert
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Grummt
authors.affiliation: Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany. Electronic address: holger.bierhoff@uni-jena.de.
authors.forename: Holger
authors.initials: H
authors.lastname: Bierhoff
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D020459:Genes, rRNA; D057809:HEK293 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000235:genetics / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D000075702:Nedd4 Ubiquitin Protein Ligases; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D006657:Histones; D009707:Nucleosomes; D062085:RNA, Long Noncoding; D011495:Histone-Lysine N-Methyltransferase; C542918:KMT5C protein, human; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618461:Nedd4l protein, mouse; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex