sh.sePublications
Change search
ReferencesLink to record
Permanent link

Direct link
Genome-wide occupancy profile of mediator and the Srb8-11 module reveals interactions with coding regions
Karolinska Institutet.
Södertörn University, School of Life Sciences. Karolinska Institutet.
Södertörn University, School of Life Sciences. Karolinska Institutet.
Institute of Molecular Biology, Copenhagen, Denmark.
Show others and affiliations
2006 (English)In: Molecular Cell, ISSN 1097-2765, E-ISSN 1097-4164, Vol. 22, no 2, 169-178 p.Article in journal (Refereed) Published
Abstract [en]

Mediator exists in a free form containing the Med12, Med13, CDK8, and CycC subunits (the Srb8-11 module) and a smaller form, which lacks these four subunits and associates with RNA polymerase II (Pol II), forming a holoenzyme. We use chromatin immunoprecipitation (ChIP) and DNA microarrays to investigate genome-wide localization of Mediator and the Srb8-11 module in fission yeast. Mediator and the Srb8-11 module display similar binding patterns, and interactions with promoters and upstream activating sequences correlate with increased transcription activity. Unexpectedly, Mediator also interacts with the downstream coding region of many genes. These interactions display a negative bias for positions closer to the 5' ends of open reading frames (ORFs) and appear functionally important, because downregulation of transcription in a temperature-sensitive med17 mutant strain correlates with increased Mediator occupancy in the coding region. We propose that Mediator coordinates transcription initiation with transcriptional events in the coding region of eukaryotic genes.

Place, publisher, year, edition, pages
2006. Vol. 22, no 2, 169-178 p.
National Category
Biochemistry and Molecular Biology Cell Biology
Identifiers
URN: urn:nbn:se:sh:diva-14301DOI: 10.1016/j.molcel.2006.03.032ISI: 000237150400007PubMedID: 16630887ScopusID: 2-s2.0-33646075157OAI: oai:DiVA.org:sh-14301DiVA: diva2:468148
Available from: 2011-12-20 Created: 2011-12-20 Last updated: 2016-08-04Bibliographically approved
In thesis
1. Genome-wide study of HDACs and transcription in Schizosaccharomyces pombe
Open this publication in new window or tab >>Genome-wide study of HDACs and transcription in Schizosaccharomyces pombe
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The eukaryotic genome has to be organized to fit into the cell and this is achieved by packing of DNA into chromatin. The basic repeating structural unit of chromatin is the nucleosome, which consists of DNA wrapped around histone proteins. Histones are subjected to multiple covalent posttranslational modifications including, acetylation, methylation, phosphorylation, and ubiquitination. These modifications take part in gene regulation by changing the structure of chromatin and by recruiting gene regulatory proteins. Histone acetylation can be removed by histone deacetylases (HDACs), which are highly conserved enzymes that regulate a diverse number of biological processes including gene expression and chromosome segregation, and have shown to be closely linked to major diseases like cancer. This thesis described the genome-wide role of HDACs and transcription in S. pombe. We studied the genome wide binding targets and enzymatic specificity of different S. pombe HDACs and uncovered different roles for the enzymes at silent regions and in repression and activation of gene expression. We proposed that independent of gene length, a typical fission yeast gene shows a 5 to 3 polarity, i.e., the histone acetylation levels peak near the ATG and gradually decrease in the coding regions. We also observed that different HDACs are responsible for different position within the ORF regions. Our genome-wide study of two different Mediator complexes reviled that they displayed similar binding patterns, and interactions with promoters and upstream activating sequences correlated with increased transcription activity. We also found that Mediator associates with the downstream coding region of many genes. We finally developed a method, E-map, which made it possible to systematically construct haploid double mutants. This method was used for constructing genome-wide genetic interaction maps of HDACs in S. pombe. From our preliminary results we discovered a new link between the Class III HDACs and a biosynthesis protein. Our data also suggest that different HDACs are involved in distinct biological processes.

Place, publisher, year, edition, pages
Stockholm: Karolinska Institutet, 2010. 51 p.
National Category
Biological Sciences
Identifiers
urn:nbn:se:sh:diva-30694 (URN)978-91-7409-970-6 (ISBN)
Supervisors
Available from: 2016-08-04 Created: 2016-08-04 Last updated: 2016-08-04Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMedScopus

Search in DiVA

By author/editor
Wirén, MariannaSinha, IndranilEkwall, Karl
By organisation
School of Life Sciences
In the same journal
Molecular Cell
Biochemistry and Molecular BiologyCell Biology

Search outside of DiVA

GoogleGoogle Scholar

Altmetric score

Total: 31 hits
ReferencesLink to record
Permanent link

Direct link