Dr Jocelyne Vreede of the Computational Chemistry group at the Van 't Hoff Institute for Molecular Sciences has received an NWO KLEIN-2 grant for a four-year project investigating how the shape and compactness of DNA affect the expression of genes. In cooperation with Prof. Willem Kegel, professor of Self-organizing Systems at Utrecht University, experimental, theoretical and computational approaches will be developed to provide quantitative and detailed insights into this as of yet unknown aspect of DNA transcription.
Transcription is the process by which a gene segment on DNA is copied into messenger RNA. At the heart of this process is RNA polymerase, a protein which reads DNA and converts the genetic information into RNA molecules. Equally important are transcription factors: proteins that either activate or repress the binding of the RNA polymerase to DNA.
A lot of progress has been made on establishing the direct influence of transcription factors by their binding to so-called promoter regions located near the genes of interest. However, transcription factors also bind to other parts of the DNA, though weakly. This suggests that the total amount of DNA available for binding will compete with the promoter regions that regulate the actual transcription for the binding of transcription factors
Somewhat surprisingly, this ‘next level’ of gene regulation has not yet been systematically addressed. Indeed, several processes in the cell influence the shape and compactness of the DNA, which will lead to significant variations in the amount of DNA that is accessible to the proteins that bind to it. Therefore, processes that alter the accessibility of DNA will, in turn, affect the expression of genes. In this project, these processes and their effect on transcription rates will be investigated experimentally and computationally.
The NWO KLEIN-2 grant will enable the appointment of two PhD students to carry out experiments (in Utrecht) and simulations (in Amsterdam) to shed more light on this unknown aspect of DNA transcription.