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The chromatin‐remodeling complexes B‐WICH and NuRD regulate ribosomal transcription in response to glucose
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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2020 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 34, no 8, p. 10818-10834Article in journal (Refereed) Published
Abstract [en]

Regulation of ribosomal transcription is under tight control from environmental stimuli, and this control involves changes in the chromatin structure. The underlying mechanism of how chromatin changes in response to nutrient and energy supply in the cell is still unclear. The chromatin‐remodeling complex B‐WICH is involved in activating the ribosomal transcription, and we show here that knock down of the B‐WICH component WSTF results in cells that do not respond to glucose. The promoter is less accessible, and RNA pol I and its transcription factors SL1/TIF‐1B and RRN3/TIF‐1A, as well as the proto‐oncogene c‐MYC and the activating deacetylase SIRT7 do not bind upon glucose stimulation. In contrast, the repressive chromatin state that forms after glucose deprivation is reversible, and RNA pol I factors are recruited. WSTF knock down results in an accumulation of the ATPase CHD4, a component of the NuRD chromatin remodeling complex, which is responsible for establishing a repressive poised state at the promoter. The TTF‐1, which binds and affect the binding of the chromatin complexes, is important to control the association of activating chromatin component UBF. We suggest that B‐WICH is required to allow for a shift to an active chromatin state upon environmental stimulation, by counteracting the repressive state induced by the NuRD complex.

Place, publisher, year, edition, pages
2020. Vol. 34, no 8, p. 10818-10834
Keywords [en]
CHD4, chromatin remodeling, c-MYC, ribosomal genes, TTF-1, WSTF
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:su:diva-184041DOI: 10.1096/fj.202000411RISI: 000546063500001OAI: oai:DiVA.org:su-184041DiVA, id: diva2:1457728
Available from: 2020-08-12 Created: 2020-08-12 Last updated: 2022-02-26Bibliographically approved
In thesis
1. RNA Polymerase I regulation by chromatin remodelling
Open this publication in new window or tab >>RNA Polymerase I regulation by chromatin remodelling
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cell proliferation and growth is correlated with effective protein synthesis and ribosome biogenesis. The transcription of the 47S pre-ribosomal RNA by RNA Polymerase I (RNA Pol I) machinery is the rate-limiting step of ribosome biogenesis and can accounts for more than 50% of total cellular transcription. RNA Polymerase I transcription is a highly energy-consuming process which requires regulation at various stages.

In the work presented in this thesis, we have investigated the regulation of RNA Pol I transcription, and investigated the stress response triggered by impaired RNA Pol I transcription. We showed in study I that the ATP dependent chromatin remodelling complex B-WICH is required to maintain an open chromatin landscape at the ribosomal DNA (rDNA) gene promoter in order to allow for transcription initiation by RNA Pol I. In absence of B-WICH, the NuRD complex reconfigures the chromatin landscape to an inaccessible state. We showed in study II that impairment of RNA Pol I transcription by deleting WSTF, a core subunit of B-WICH resulted in cell cycle arrest and apoptosis. More severe inhibition of RNA Pol I transcription through chemical compounds resulted in activation of cellular stress response cascades including but not limited to cell cycle arrest, unfolded protein response and oxidative stress response. We showed in study III that RNA Pol I transcription was increased during epithelial-mesenchymal transition (EMT) in the context of development and disease. The association of the EMT-driving transcription factor SNAIL1 with the rDNA gene promoter was shown to be essential in EMT triggered RNA Pol I transcription. The work presented in this thesis demonstrates the importance of RNA Pol I transcription regulation in maintaining cellular homeostasis.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2020. p. 55
Keywords
RNA Pol I, ribosome genes, chromatin remodelling, WSTF, CHD4
National Category
Cell Biology
Research subject
Molecular Bioscience
Identifiers
urn:nbn:se:su:diva-184045 (URN)978-91-7911-210-3 (ISBN)978-91-7911-211-0 (ISBN)
Public defence
2020-09-25, Vivi Täckholmsalen (Q-salen), NPQ-huset, Svante Arrhenius väg 20, Stockholm, 09:00 (English)
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Available from: 2020-09-02 Created: 2020-08-12 Last updated: 2022-02-26Bibliographically approved

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Rolicka, AnnaGuo, YuanGañez Zapater, AntoniTariq, KanwalQuin, JaclynÖstlund Farrants, Ann‐Kristin

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Rolicka, AnnaGuo, YuanGañez Zapater, AntoniTariq, KanwalQuin, JaclynÖstlund Farrants, Ann‐Kristin
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