Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
The B-WICH chromatin-remodelling complex initiates the regulation of RNA polymerase III by c-Myc
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.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Transcription by RNA polymerase III in eukaryotic cells is closely associated with cell growth and proliferation, and regulated by several proliferative signals. In addition, the chromatin-remodelling complex B-WICH, comprised of William syndrome transcription factor, the ATPase SNF2h and nuclear myosin, binds to the 5S rRNA and 7SL genes and activates transcription, but the mechanism behind is poorly understood. Here, we have used high‑resolution MN walking to show that the role of B-WICH in RNA polymerase III transcription is to induce local alterations of the chromatin structure in the vicinity of the 5S rRNA and 7SL RNA genes. In the 5S rDNA, the remodelled region harbours an E-box, to which c-Myc, together with Max, binds in a B-WICH dependent way.  Both B-WICH and c-Myc are required for the subsequent histone acetylation of histone H3. Our results present two ways for c-Myc to alter 5S rRNA transcription; to bind to the RNA polymerase III machinery at the promoter and to an E-box in the intergenic spacer. We propose a model in which the B-WICH complex is required to maintain an open chromatin structure at these RNA polymerase III genes, which is a prerequisite for other regulatory factors to bind at the gene.

National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-103000OAI: oai:DiVA.org:su-103000DiVA: diva2:714260
Available from: 2014-04-25 Created: 2014-04-25 Last updated: 2016-01-29Bibliographically approved
In thesis
1. Non-protein-coding RNA: Transcription and regulation of ribosomal RNA
Open this publication in new window or tab >>Non-protein-coding RNA: Transcription and regulation of ribosomal RNA
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cell growth and proliferation are processes in the cell that must be tightly regulated. Transcription of ribosomal RNA and ribosomal biogenesis are directly linked to cell growth and proliferation, since the ribosomal RNA encodes for the majority of transcription in a cell and ribosomal biogenesis influences directly the number of proteins that are synthesized.

In the work presented in this thesis, we have investigated the ribosomal RNA genes, namely the ribosomal DNA genes and the 5S rRNA genes, and their transcriptional regulation. One protein complex that is involved in RNA polymerase I and III transcription is the chromatin remodelling complex B‑WICH (WSTF, SNF2h, NM1). RNA polymerase I transcribes the rDNA gene, while RNA polymerase III transcribes the 5S rRNA gene, among others. In Study I we determined the mechanism by which B‑WICH is involved in regulating RNA polymerase I transcription. B‑WICH is associated with the rDNA gene and was able to create a more open chromatin structure, thereby facilitating the binding of HATs and the subsequent histone acetylation. This resulted in a more active transcription of the ribosomal DNA gene. In Study II we wanted to specify the role of NM1 in RNA polymerase I transcription. We found that NM1 is not capable of remodelling chromatin in the same way as B‑WICH, but we demonstrated also that NM1 is needed for active RNA polymerase I transcription and is able to attract the HAT PCAF. In Study III we investigated the intergenic part of the ribosomal DNA gene. We detected non-coding RNAs transcribed from the intergenic region that are transcribed by different RNA polymerases and that are regulated differently in different stress situations. Furthermore, these ncRNAs are distributed at different locations in the cell, suggesting that they have different functions. In Study IV we showed the involvement of B‑WICH in RNA Pol III transcription and, as we previously had shown in Study I, that B‑WICH is able to create a more open chromatin structure, in this case by acting as a licensing factor for c-Myc and the Myc/Max/Mxd network.

Taken together, we have revealed the mechanism by which the B‑WICH complex is able to regulate RNA Pol I and Pol III transcription and we have determined the role of NM1 in the B‑WICH complex. We conclude that B‑WICH is an important factor in the regulation of cell growth and proliferation. Furthermore, we found that the intergenic spacer of the rDNA gene is actively transcribed, producing ncRNAs. Different cellular locations suggest that the ncRNAs have different functions.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2014. 58 p.
Keyword
ribosomal RNA, non-coding RNA, ribosomal genes, rDNA gene, B-WICH, chromatin remodelling, histone modification
National Category
Cell Biology
Research subject
Cell Biology
Identifiers
urn:nbn:se:su:diva-102718 (URN)978-91-7447-906-5 (ISBN)
Public defence
2014-05-23, Lecture hall E306, Arrheniuslaboratorierna, Svante Arrhenius Väg 20 C, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defence the following papers were unpublished and had a status as follows: Paper 2: Manuscript; Paper 3: Manuscript

Available from: 2014-04-29 Created: 2014-04-16 Last updated: 2014-04-29Bibliographically approved

Open Access in DiVA

No full text

Search in DiVA

By author/editor
Böhm, StefanieVintermist, AnnaÖstlund Farrant, Ann-Kristin
By organisation
Department of Molecular Biosciences, The Wenner-Gren Institute
Biological Sciences

Search outside of DiVA

GoogleGoogle Scholar

urn-nbn

Altmetric score

urn-nbn
Total: 31 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf