Quiescence-Induced LncRNAs Trigger H4K20 Trimethylation and Transcriptional Silencing

Bierhoff, Holger; Dammert, Marcel A.; Brocks, David; Dambacher, Silvia; Schotta, Gunnar; Grummt, Ingrid

doi:10.1016/j.molcel.2014.03.032

Cited by 148 publications

(144 citation statements)

References 31 publications

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“…Consistent with these findings, the expression of JHDM1B/KDM2B, a JmjC demethylase that is found in the nucleolus and that is required for rDNA silencing, is significantly downregulated in glioblastoma (84). In parallel, H4K20me3 at rDNA loci is downregulated in breast and colon cancer cells (80). However, in contrast to these examples, knockdown of the PHF8/JKDM7B JmjC demethylase decreases pre-rRNA synthesis and leads to reduced proliferation of osteosarcoma cells (86).…”

Section: Disease Progressionsupporting

confidence: 53%

“…Moreover, SUV39H1, a component of the eNoSC, mediates H3K9me2, allowing rDNA silencing during glucose deprivation (53,79). The level of SUV4-20H2-catalyzed H4K20me3 is increased at rDNA regions during growth arrest in NIH 3T3 cells (80). PAPAS (promoter and prerRNA antisense) is a long noncoding RNA that is produced in an antisense orientation by RNA polymerase II (RNAPII) and covers sequences of the pre-rRNA coding region and the rDNA promoter (81).…”

Section: Involvement Of Histone Modifications In Rdna Silencing Histomentioning

confidence: 99%

“…PAPAS (promoter and prerRNA antisense) is a long noncoding RNA that is produced in an antisense orientation by RNA polymerase II (RNAPII) and covers sequences of the pre-rRNA coding region and the rDNA promoter (81). This noncoding RNA is upregulated in growtharrested cells and is accompanied by increased SUV4-20H2-mediated H4K20me3 and chromatin compaction (80,81). Additionally, PRMT5, the type II arginine methyltransferase that catalyzes monomethylation or symmetric dimethylation of histones H3 and H4, plays a key role in silencing rDNA when the cells are in a stationary or nonproliferating state (82).…”

Section: Involvement Of Histone Modifications In Rdna Silencing Histomentioning

confidence: 99%

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The Epigenetic Pathways to Ribosomal DNA Silencing

Srivastava

Ahn

2016

Microbiol Mol Biol Rev

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SUMMARYHeterochromatin is the transcriptionally repressed portion of eukaryotic chromatin that maintains a condensed appearance throughout the cell cycle. At sites of ribosomal DNA (rDNA) heterochromatin, epigenetic states contribute to gene silencing and genome stability, which are required for proper chromosome segregation and a normal life span. Here, we focus on recent advances in the epigenetic regulation of rDNA silencing inSaccharomyces cerevisiaeand in mammals, including regulation by several histone modifications and several protein components associated with the inner nuclear membrane within the nucleolus. Finally, we discuss the perturbations of rDNA epigenetic pathways in regulating cellular aging and in causing various types of diseases.

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Section: Disease Progressionsupporting

confidence: 53%

Section: Involvement Of Histone Modifications In Rdna Silencing Histomentioning

confidence: 99%

Section: Involvement Of Histone Modifications In Rdna Silencing Histomentioning

confidence: 99%

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The Epigenetic Pathways to Ribosomal DNA Silencing

Srivastava

Ahn

2016

Microbiol Mol Biol Rev

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“…Recent reports also suggest that signal transduction pathways control the epigenetic states of rDNA (6). For example, while histone methylation, a key type of histone modification, plays a central role in epigenetic regulation (23), growth factor deprivation leads to upregulation of long noncoding RNAs (lncRNAs), recruitment of the H4K20 methyltransferase Suv4-20h2 with lncRNAs to rDNA, increased H4K20me3 levels, and compaction of chromatin (24). Manipulation of chromatin structures has been thought to be a novel therapy for cancer (25,26), and further information on the control mechanisms of rDNA chromatin structures by signal transduction pathways would contribute to these therapies.…”

mentioning

confidence: 99%

Mild Glucose Starvation Induces KDM2A-Mediated H3K36me2 Demethylation through AMPK To Reduce rRNA Transcription and Cell Proliferation

Tanaka

Yano

Ogasawara

et al. 2015

Molecular and Cellular Biology

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c Environmental conditions control rRNA transcription. Previously, we found that serum and glucose deprivation induces KDM2A-mediated H3K36me2 demethylation in the rRNA gene (rDNA) promoter and reduces rRNA transcription in the human breast cancer cell line MCF-7. However, the molecular mechanism and biological significance are still unclear. In the present study, we found that glucose starvation alone induced the KDM2A-dependent reduction of rRNA transcription. The treatment of cells with 2-deoxy-D-glucose, an inhibitor of glycolysis, reduced rRNA transcription and H3K36me2 in the rDNA promoter, both of which were completely dependent on KDM2A in low concentrations of 2-deoxy-D-glucose, that is, mild starvation conditions. The mild starvation induced these KDM2A activities through AMP-activated kinase (AMPK) but did not affect another AMPK effector of rRNA transcription, TIF-IA. In the triple-negative breast cancer cell line MDA-MB-231, the mild starvation also reduced rRNA transcription in a KDM2A-dependent manner. We detected KDM2A in breast cancer tissues irrespective of their estrogen receptor, progesterone receptor, and HER2 status, including triple-negative cancer tissues. In both MCF-7 and MDA-MB-231 cells, mild starvation reduced cell proliferation, and KDM2A knockdown suppressed the reduction of cell proliferation. These results suggest that under mild glucose starvation AMPK induces KDM2A-dependent reduction of rRNA transcription to control cell proliferation. R egulation of cell growth ultimately depends on the control of new ribosome synthesis, and the rate of ribosome synthesis is tightly regulated in mammalian cells (1). Three of the four structured ribosomal RNA (rRNA) molecules constituting a ribosome are produced by processing a precursor transcript, pre-rRNA. The pre-rRNA is coded by rRNA genes (rDNA) and specifically transcribed by RNA polymerase I (Pol I) in the nucleolus (1-5). Ribosome biogenesis is limited by rRNA transcription, and the control of rRNA transcription is thought to play a central role in the regulation of ribosome biogenesis and cell growth (6-9). The rRNA transcription is dysregulated during tumorigenesis, and selective inhibition of rRNA transcription may offer a therapeutic strategy to block cancer cell proliferation (3, 10, 11).The level of rRNA transcription is controlled by environmental conditions (11). To date, increasing numbers of studies have revealed that the signal transduction pathways reach the rRNA transcription machinery in the nucleolus and regulate rRNA transcription (7,9,(12)(13)(14). Some signal pathways control the activities of basic transcription factors for Pol I (2). For example, mitogen-activated protein kinase (MAPK) signaling, the mammalian target of rapamycin signaling, and type 1 insulin-like growth factor activate rRNA transcription through upstream binding factor, selectivity factor 1 and/or transcription initiation factor IA (TIF-IA, the mammalian homolog of yeast Rrn3) (15-21). AMP-activated kinase (AMPK), a sensor to maintain energy homeo...

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“…The elevated level of H4K20me3 leads to chromatin compaction. The lncRNAs are antisense transcripts against rDNA, are termed the promoter and pre-rRNA antisense (PAPAS), and associated with rDNA [38].…”

Section: Control Of Rrna Transcription By Unidentified Serum Factorsmentioning

confidence: 99%

Control of Ribosomal RNA Transcription by Nutrients

Tanaka¹,

Tsuneoka²

2018

Gene Expression and Regulation in Mammalian Cells - Transcription Toward the Establishment of Novel Therapeutics

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The ribosome is a unique machine for protein synthesis in organisms. The construction of ribosomes is exceedingly complex and consumes the majority of the cell materials and energy. The materials for ribosome production are supplied by nutrients. Therefore, the production of ribosomes is restricted by environmental nutrients, and cells need mechanisms to control ribosome production in order to reconcile demands for cell activities with available resources. Transcription of ribosomal RNA is an essential step in ribosome biogenesis. It strongly affects the total amount of ribosome production, and thus rapidly growing cells have an elevated level of ribosomal RNA transcription. Ribosomal RNA transcription is controlled by many mechanisms, including the efficiency of preinitiation complex formation for RNA polymerase I (Pol I) and epigenetic marks in ribosomal RNA genes. These are affected by cell cycle progression, signal transduction pathways, cell-damaging stresses, nutrients such as glucose, and the metabolites. Recent studies also suggest that the epigenetic marks, acetylation and methylation, may be not only controlled by nutrients but also function as reservoirs for biological resources in chromatin. Further studies would provide information about the mechanisms cells use to adjust production of cellular components to available resources and clues for developing novel anti-cancer treatments.

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Quiescence-Induced LncRNAs Trigger H4K20 Trimethylation and Transcriptional Silencing

Cited by 148 publications

References 31 publications

The Epigenetic Pathways to Ribosomal DNA Silencing

The Epigenetic Pathways to Ribosomal DNA Silencing

Mild Glucose Starvation Induces KDM2A-Mediated H3K36me2 Demethylation through AMPK To Reduce rRNA Transcription and Cell Proliferation

Control of Ribosomal RNA Transcription by Nutrients

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