Growth Factor Signaling Regulates Elongation of RNA Polymerase I Transcription in Mammals via UBF Phosphorylation and r-Chromatin Remodeling

Stefanovsky, Victor Y.; Langlois, Frédèric; Gagnon-Kugler, Thérèse; Rothblum, L; Moss, Tom

doi:10.1016/j.molcel.2006.01.023

Cited by 191 publications

(204 citation statements)

References 49 publications

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“…1). As expected, over 50% of cells were in G 1 , and approximately 25% were in S phase at t = 0, before the cells were released from the double thymidine block. At 3 hours following release (t =3) the majority of cells had moved completely into S phase, while 6 hours following release (t = 6) cells were either in late S phase or entering G 2 .…”

Section: Resultssupporting

confidence: 80%

“…27 Previous studies have found that the DNA content of HeLa cells is slowly increasing during thymidine treatment, indicating that the cells rather than being completely inhibited at G 1 /S are actually progressing very slowly in early S phase. 32,34 Thus our results indicate a considerable decrease in DNA methylation upon entrance to S and oscillations in the levels of DNA methylation as the cells progress through S, with a remethylation in G 2 and G 1 .…”

Section: Resultssupporting

confidence: 54%

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Dynamic epigenetic states of ribosomal RNA promoters during the cell cycle

Brown

Szyf²

2008

Cell Cycle

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Section: Resultssupporting

confidence: 80%

Section: Resultssupporting

confidence: 54%

Dynamic epigenetic states of ribosomal RNA promoters during the cell cycle

Brown

Szyf²

2008

Cell Cycle

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“…Altogether, the SRM-like I-DIRT approach, co-localization, and reciprocal immunopurifications confirmed the SIRT7 interaction with Pol I, UBF, and components of the B-WICH complex. (41); however, increased transcription is not due to an increased number of actively transcribed rDNA units but instead is due to changes in the rate of transcription, especially of elongation (42,43). B-WICH is an ATP-dependent chromatin remodeling complex containing SNF2h, a human ISWI ATPase, and it was shown to associate with Pol I facilitating its transcription (30).…”

Section: Discussionmentioning

confidence: 99%

Functional Proteomics Establishes the Interaction of SIRT7 with Chromatin Remodeling Complexes and Expands Its Role in Regulation of RNA Polymerase I Transcription

Tsai¹,

Greco²,

Boonmee

et al. 2012

Molecular & Cellular Proteomics

121

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Among mammalian sirtuins, SIRT7 is the only enzyme residing in nucleoli where ribosomal DNA is transcribed. Recent reports established that SIRT7 associates with RNA Pol I machinery and is required for rDNA transcription. Although defined by its homology to the yeast histone deacetylase Sir2, current knowledge suggests that SIRT7 itself has little to no deacetylase activity. Because only two SIRT7 interactions have been thus far described: RNA Pol I and upstream binding factor, identification of proteins and complexes associating with SIRT7 is critical to understanding its functions. Here, we present the first characterization of SIRT7 interaction networks. We have systematically investigated protein interactions of three EGFP-tagged SIRT7 constructs: wild type, a point mutation affecting rDNA transcription, and a deletion mutant lacking the predicted coiled-coil domain. A combinatorial proteomics and bioinformatics approach was used to integrate gene ontology classifications, functional protein networks, and normalized abundances of proteins coisolated with SIRT7. The resulting refined proteomic data set confirmed SIRT7 interactions with RNA Pol I and upstream binding factor and highlighted association with factors involved in RNA Pol I-and II-dependent transcriptional processes and several nucleolus-localized chromatin remodeling complexes. Particularly enriched were members of the B-WICH complex, such as Mybbp1a, WSTF, and SNF2h. Prominent interactions were validated by a selected reaction monitoring-like approach using metabolic labeling with stable isotopes, confocal microscopy, reciprocal immunoaffinity precipitation, and co-isolation with endogenous SIRT7. To extend the current knowledge of mechanisms involved in SIRT7-dependent regulation of rDNA transcription, we showed that small interfering RNA-mediated SIRT7 knockdown leads to reduced levels of RNA Pol I protein, but not messenger RNA, which was confirmed in diverse cell types. The correlation between histone acetylation status and transcriptional regulation is well established in that hyperacetylation is commonly associated with transcriptional activation, whereas hypoacetylation is associated with transcriptional repression (1-3). In eukaryotes, Sir2-like proteins form a family of enzymes known as sirtuins (4). Distinct from class I and II histone deacetylases (HDACs), which facilitate hydrolysis of acetyl-lysine as a bimolecular reaction (5), sirtuins consume an equimolar amount of nicotinamide adenine dinucleotide (NAD ϩ ) for each hydrolysis reaction and generate nicotinamide, O-acetyl ADP-ribose, and deacetylated substrate as end products (4). Based on homology of the sirtuin core domain, there are seven sirtuins (SIRT1-7) in human cells with functions not limited to histone deacetylation, because many additional cellular proteins have been identified as substrates (4, 6). In addition, the localizations of human sirtuins are distributed across multiple organelles including nucleolus, nucleus, cytoplasm, and mitochondria (7).Systematic monitorin...

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“…19), transcription elongation (17,18), rRNA processing, and assembly (20 -22). To identify novel regulators of rRNA gene synthesis, we screened for factors interacting with RNA Pol I.…”

mentioning

confidence: 99%

Myb-binding Protein 1a (Mybbp1a) Regulates Levels and Processing of Pre-ribosomal RNA

Hochstatter

Hölzel

Michaela

et al. 2012

Journal of Biological Chemistry

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Background: rRNA gene transcription and processing have to be coordinated, as they are intimately linked. Results: Mybbp1a regulates RNA Pol I transcription and pre-rRNA processing. Conclusion: Mybbp1a coordinates both processes. Significance: Mybbp1a was shown to be an important regulator of cellular proliferation, related to RNA Pol II genes. We link its function now as well to regulating RNA Pol I genes and to control ribosome biogenesis.

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Growth Factor Signaling Regulates Elongation of RNA Polymerase I Transcription in Mammals via UBF Phosphorylation and r-Chromatin Remodeling

Cited by 191 publications

References 49 publications

Dynamic epigenetic states of ribosomal RNA promoters during the cell cycle

Dynamic epigenetic states of ribosomal RNA promoters during the cell cycle

Functional Proteomics Establishes the Interaction of SIRT7 with Chromatin Remodeling Complexes and Expands Its Role in Regulation of RNA Polymerase I Transcription

Myb-binding Protein 1a (Mybbp1a) Regulates Levels and Processing of Pre-ribosomal RNA

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