New thesis examines key aspects of cellular quiescence

What is the main focus of your thesis?

Cellular quiescence is a reversible, non-proliferative state in which cells temporarily exit the cell cycle while retaining the ability to re-enter it upon receiving appropriate cues. This state allows cells to endure unfavorable environmental conditions and protects them from stress-induced damage.

During my PhD, I used fission yeast as a model to investigate key aspects of quiescence, including entry potential, chromosome condensation, genome-wide transcriptional reprogramming, histone modification dynamics, and three-dimensional genome architecture.

Our overarching goal was to uncover the mechanisms by which transcriptional programs and epigenomic landscapes are dynamically reorganized during both the initiation and long-term maintenance of quiescence.

Which are the most important results?

We identified 149 genes that are significantly upregulated during early quiescence, contrasting with the global downregulation of transcriptional activity across the genome. Among these, 16 genes maintained high expression levels from early to late quiescence and were predominantly located in subtelomeric regions. ChIP-seq profiling revealed a strong association between these genes and the active histone modification H3K4me3. Notably, H3K4me3 was found to regulate RNA polymerase II (RNAPII) pausing at promoter-proximal regions, with its deposition dependent on Set1, the catalytic subunit of the COMPASS complex. Complementary Hi-C analysis revealed the formation of highly interactive topologically associating domains (TADs) in subtelomeric regions, accompanied by telomere hyper-clustering—a structural hallmark reminiscent of quiescent genome architecture observed in other eukaryotic systems.

How can this new knowledge contribute to the improvement of people’s health?

Since quiescence is a common cellular state found in many cell types—including stem cells and cancer cells—we hope our findings will inspire further research into the behavior and regulation of dormant cells in these contexts.

What are your future ambitions? 

Building on this study, my ambition is to further investigate how chromatin architecture and epigenetic modifications regulate gene expression during cellular quiescence in mammalian systems, in order to solidify and extend our findings. 

Dissertation

Thursday, 5 June at 09:00, Gene in Neo, Blickagången 16, Flemingsberg.

Thesis

Investigation of epigenome changes in quiescent fission yeast cells