Prof. Dr. Joachim Griesenbeck
University of Regensburg

Prof. Dr. Hinrich Boeger
University of California, Santa Cruz
Molecular Cell & Developmental Biology

Molecular mechanism of gene activation: Chromatin transition at the yeast PHO5 promoter.

In any organism transcription has to be orchestrated in order to entertain the complex network of cellular processes. In Eukaryotes transcriptional regulation occurs in the context of chromatin. Over the last two decades evidence has been collected that chromatin structure contributes to the control of gene expression.

We have focused on the PHO5 promoter of S. cerevisiae as a model to investigate the chromatin rearrangement occurring at this region during transcriptional activation of the gene. Our most recent work led to a mathematical model for the chromatin transition and defines the starting point for the proposed research: The model predicts a dynamic equilibrium between nucleosome removal and reassembly at the promoter, it also suggests a mechanism by which enzymes responsible for removal act on their substrate. We will experimentally address these points.

Final report:

During the last funding period by BaCaTeC the project "Molecular mechanism of gene activation: Chromatin transition at the yeast PHO5 promoter" has made major advances. Our work on a mathematical model describing the chromatin transition at the yeast PHO5 promoter was recently published in a prominent international journal (Boeger et al., 2008). In addition, we have initiated new projects to experimentally test our hypotheses derived from the above theory.

The travel funds were used for exchanges in both directions. German scientists were visiting the University of Santa Cruz twice in autumn 2007 and spring 2008, for two weeks each. Besides performing experimental work we were profiting from intensive discussions and theoretical exchange. Finally, a visit from Santa Cruz scientists at the University of Regensburg in June 2008 served to define the status quo of the work and to delineate the future perspective.

Boeger, H., Griesenbeck, J., and Kornberg, R. D. (2008). Nucleosome retention and the stochastic nature of promoter chromatin remodeling for transcription. Cell 133, 716-726.