The Svedberg Award 2002
Stefan Björklund
Department of Medical Biochemistry and Biophysics, Umeå University
Transcriptional regulation in eukaryots
Background
I got my undergraduate training in medicine at Umeå University. As a
graduate student, I studied the cell cycle regulated expression of
mammalian ribonucleotide reductase together with Professor Lars
Thelander and the Department of Medical Biochemistry and Biophysics,
Umeå University. This work included characterization of the mouse
ribonucleotide reductase subunit R1 and R2 promoters and the expression
of the corresponding mRNAs through the cell cycle. In 1993 I received
an EMBO long-term post-doc fellowship to study transcriptional
regulation with Professor Roger Kornberg at the Department of Cell
Biology, Stanford University and I returned to Sweden in 1995 to build
up my own research group.
Studies of general mechanisms in yeast
RNA Polymerase transcribes genetic information into a message that can
be read by the ribosome to produce protein. Transcription is the first
step and a key control point in gene expression. Transcriptional
regulation underlies all aspects of cellular metabolism including
oncogenesis (cancer) and morphogenesis (development).
We study how transcription regulatory proteins work. These types of
proteins generally bind sequence-specifically to consensus DNA
sequences present in promoters. They can then affect the general
transcription machinery (RNA polymerase II and its associated general
transcription factors (GTF´s), TBP, TFIIB, TFIIE, TFIIF, and TFIIH). In
collaboration with other groups, we have identified a protein complex
composed of 20 subunits called the Mediator. Mediator is essential to
confer signals from the regulatory proteins to the general
transcription factors.
We are presently studying how different regulatory proteins contact
Mediator subunits and also how the mediator subunits interact to form
the complex.
S-phase-specific transcriptional activation in mouse cells.
Our second project concerns S-phase-specific transcriptional activation
in mouse cells. It has been shown that yeast cells coordinate
expression of S-phase-specific genes by binding one of two different
activator proteins to their promoters. However, no such universal
S-phase-specific activator has been identified in higher eukaryotic
cells. We have therefore recently developed an in vitro transcription
system composed of highly purified mouse RNA polymerase II and GTF´s.
We are now in a position to study different S-phase-specific promoters
in this system and to use it for biochemical purification and
identification of factors that control, and possibly coordinate,
activation of these promoters.