Stefan Björklund - Professor

The Mediator complex and its function in transcriptional regulation at the molecular level

Tumor development is usually caused by changes of the levels, the expression pattern or the activity for one or several proteins. These changes are often a result of mutations of certain genes i.e. proto-oncogenes and tumor suppressor genes. These genes normally function as a template for the synthesis of proteins that in the normal, healthy cell function as master regulators of larger families of genes. Another function for proto-oncogenes and tumor suppressor genes is to encode for proteins that control cell division. This process must proceed in a controlled manner where one process must be completed before the next process is initiated. A common cause for tumor development is mutations in the genes that encode these control proteins which then leads to miss-expression of other proteins and uncontrolled cell division. Knowledge about the basic mechanisms that control how transcription is regulated is therefore fundamental to reveal the underlying mechanisms behind most tumors, and in the long run for the possibility to develop drugs to treat different cancer.


In this project we combine structural and functional studies of a set of ~25 proteins which assemble in a large complex called Mediator. The mediator complex is essential for regulated transcription of nearly all genes in all eukaryotes from yeast to humans by transferring signals from promoter-bound transcriptional regulators to the general RNA polymerase II transcription machinery. Our aim is to reveal how Mediator functions at the molecular level in order to understand (and to influence) how transcription of genes is regulated.


We have chosen to work with two different model systems; the yeast Saccharomyces cerevisiae and the plant Arabidopsis thaliana. There are several reasons for this choice. First, basic mechanisms like replication, transcription and translation are usually well conserved between eukaryotes. Second, these systems are well suited for these types of studies. Yeast has the advantage of being easily manipulated by genetic methods which combined with biochemical methods offer unique possibilities to reveal complicated mechanisms. The plant system is interesting for studies of transcriptional regulation since plants, different to most other organisms, cannot respond to harsh environments by movement, but rather has to adapt by changing their gene expression pattern.

Group:
Céline Davoine
Jeanette Blomberg
Huahong Wang
Rajesh Kumar
Nils Elfving

Publications

Author

Title

Year sorteringsordning

Fulltext

Fallath, Thorya
Kidd, Brendan N.
Stiller, Jiri; et al.

MEDIATOR18 and MEDIATOR20 confer susceptibility to Fusarium oxysporum in Arabidopsis thaliana
PLoS ONE, 12(4)

2017

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Shaikhali, Jehad
Davoine, Céline
Björklund, Stefan; et al.

Redox regulation of the MED28 and MED32 mediator subunits is important for development and senescence
Protoplasma, 253(3): 957-963

2016

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Shaikhali, Jehad
Davoine, Celine
Brännström, Kristoffer; et al.

Biochemical and redox characterization of the mediator complex and its associated transcription factor GeBPL, a GLABROUS1 enhancer binding protein
Biochemical Journal, 468(3): 385-400

2015

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Broach, James R
Bharatula, Vasudha
Chereji, Razvan; et al.

The Msn2 mediated stress response: Survival based on "hedging your bet" and a dynamic interplay of transcription factor binding and nucleosome occupancy
Yeast, 32(Suppl. 1): S221-S222

2015

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Elfving, Nils
Chereji, Razvan V.
Bharatula, Vasudha; et al.

A dynamic interplay of nucleosome and Msn2 binding regulates kinetics of gene activation and repression following stress
Nucleic Acids Research, 42(9): 5468-5482

2014

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Aguilar, Ximena
Blomberg, Jeanette
Brännström, Kristoffer; et al.

Interaction Studies of the Human and Arabidopsis thaliana Med25-ACID Proteins with the Herpes Simplex Virus VP16-and Plant-Specific Dreb2a Transcription Factors
PLoS ONE, 9(5): e98575-

2014

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Larsson, Miriam
Uvell, Hanna
Sandström, Jenny; et al.

Functional Studies of the Yeast Med5, Med15 and Med16 Mediator Tail Subunits
PLoS ONE, 8(8): e73137-

2013

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Blomberg, Jeanette
Aguilar, Ximena
Brännström, Kristoffer; et al.

Interactions between DNA, transcriptional regulator Dreb2a and the Med25 mediator subunit from Arabidopsis thaliana involve conformational changes
Nucleic Acids Research, 40(13): 5938-5950

2012

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Elfving, Nils
Davoine, Céline
Benlloch, Reyes; et al.

The Arabidopsis thaliana Med25 mediator subunit integrates environmental cues to control plant development
Proceedings of the National Academy of Sciences of the United States of America, 108(20): 8245-8250

2011

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Shaikhibrahim, Zaki
Rahaman, Hamidur
Wittung-Stafshede, Pernilla; et al.

Med8, Med18, and Med20 subunits of the Mediator head domain are interdependent upon each other for folding and complex formation
Proceedings of the National Academy of Sciences of the United States of America, 106(49): 20728-20733

2009

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Stefan Björklund

Contact Information

Umeå University
Medical Biochemistry and Biophysics
SE-901 87 Umeå, SWEDEN 

Visiting Address
KBC-building, 6th floor

Tel:  +46 90 786 6788

Fax:  +46 90 786 9795

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