lncRNA-Induced Nucleosome Repositioning Reinforces Transcriptional Repression of rRNA Genes upon Hypotonic Stress

Zhongliang Zhao; Marcel Andre Dammert; Ingrid Grummt; Holger Bierhoff

doi:10.1016/j.celrep.2016.01.073

lncRNA-Induced Nucleosome Repositioning Reinforces Transcriptional Repression of rRNA Genes upon Hypotonic Stress

Cell Rep. 2016 Mar 1;14(8):1876-82. doi: 10.1016/j.celrep.2016.01.073. Epub 2016 Feb 18.

Authors

Zhongliang Zhao¹, Marcel Andre Dammert¹, Ingrid Grummt¹, Holger Bierhoff²

Affiliations

¹ Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
² 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.

PMID: 26904956
DOI: 10.1016/j.celrep.2016.01.073

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Chromatin Assembly and Disassembly
Endosomal Sorting Complexes Required for Transport / genetics*
Endosomal Sorting Complexes Required for Transport / metabolism
Gene Expression Regulation
Genes, rRNA*
HEK293 Cells
Histone-Lysine N-Methyltransferase / genetics*
Histone-Lysine N-Methyltransferase / metabolism
Histones / genetics
Histones / metabolism
Humans
Mi-2 Nucleosome Remodeling and Deacetylase Complex / genetics
Mi-2 Nucleosome Remodeling and Deacetylase Complex / metabolism
Mice
NIH 3T3 Cells
Nedd4 Ubiquitin Protein Ligases
Nucleosomes / chemistry*
Nucleosomes / metabolism
Nucleosomes / ultrastructure
Osmolar Concentration
Osmotic Pressure*
Proteasome Endopeptidase Complex / metabolism
Proteolysis
RNA, Long Noncoding / genetics*
RNA, Long Noncoding / metabolism
Signal Transduction
Transcription, Genetic
Ubiquitin-Protein Ligases / genetics*
Ubiquitin-Protein Ligases / metabolism
Ubiquitination

Substances

Endosomal Sorting Complexes Required for Transport
Histones
Nucleosomes
RNA, Long Noncoding
Histone-Lysine N-Methyltransferase
KMT5C protein, human
Nedd4 Ubiquitin Protein Ligases
Nedd4 protein, human
Nedd4l protein, mouse
Ubiquitin-Protein Ligases
Proteasome Endopeptidase Complex
Mi-2 Nucleosome Remodeling and Deacetylase Complex