|
Project 4: Chromatin as a regulator of genome evolution
Promotor: Yves Van de Peer, VIB Dept. of Plant Systems Biology, Ghent University
Co-promotor: Kevin Verstrepen, VIB Lab of Systems Biology, K.U.Leuven
Keywords:
Host University: Ghent University
Biological question
Eukaryotic DNA is wrapped around specific proteins called nucleosomes. The double stranded DNA wraps twice around each nucleosome, taking 147 nucleotides, followed by a variable number of "spacer" nucleotides in-between two consecutive nucleosomes. The resulting structure, called chromatin, is known to influence the transcriptional activity of genes. The basic principle of the higher-order regulation is fairly simple: stretches of DNA that are wrapped around a nucleosome are less accessible and can therefore not be bound by transcription factors. Interestingly, the exact positioning of nucleosomes is relatively stable and inherited when cells divide. However, chromatin structure can be actively or passively adapted in response to cellular physiology and environmental changes.
In this project, we will investigate whether this semi-robust chromatin structure also affects other genomic processes besides transcription. More specifically, we will ask whether chromatin affects how genomes evolve. We hypothesize that chromatin packaging may limit recombination rates at certain, densely packaged loci, while other, more open loci may favor DNA breaks and/or rearrangements. Moreover, local chromatin may also influence the transcriptional activity of inserted and rearranged DNA, which may further limit the possible places for successful genomic rearrangements and even help maintain synteny.
Basic strategy and organization
The development of novel technologies (ChIP-chip, next-generation sequencing) has enabled researchers to determine the exact position of each nucleosome in the entire genome of the model eukaryote Saccharomyces cerevisiae (brewer´s yeast). We will use a combination of computational biology, bioinformatics and experiments to study the role of chromatin in genome evolution. We will use available data to correlate nucleosomes positioning with breakpoints of chromosomal rearrangements (crossover, transposon insertion, breaks). The found correlations will be experimentally controlled using the experimental toolbox of S. cerevisiae (transformation, induced DNA break, next-gen sequencing, qPCR…)
The project will be carried out under the guidance of Yves van de Peer (VIB group Bioinformatics and Evolutionary Genomics, 50%), who is an expert in bioinformatics and sequence analysis, and the lab of Kevin verstrepen (VIB lab for systems biology, 50%), who offers expertise in S. cerevisiae gene technology and biochemistry.
|