Laboratory Valentin Flury
Chromatin dynamics across the cell cycle
The Flury lab is interested in dissecting the regulatory mechanisms maintaining epigenetic (chromatin) states across the cell cycle using genomic and proteomic approaches with high temporal and spatial resolution. We track these chromatin states over time after intrinsic challenges such as DNA replication, mitosis or DNA damage to reveal the governing principles of chromatin plasticity and stability during homeostasis, differentiation and diseased states.
Multicellular organisms display an impressive variety of different cell types even though they all contain the same genetic information. This difference is in part controlled by their epigenome, or more specifically, by chromatin states that regulate and maintain cell type-specific gene expression programs. Yet, chromatin undergoes dramatic alterations during each cell division, especially during DNA replication, where chromatin is disrupted to allow DNA synthesis. We strive to understand how chromatin states are propagated, restored, and regulated during this process and to what extent their deregulation contributes to changes in cell identity in both healthy and diseased cells.
Goals
We aim to achieve the following goals to obtain mechanistic insights into epigenome maintenance and propagation: i) Identify factors involved in epigenome propagation during DNA replication; ii) Dissect common and cell type-specific principles of chromatin restoration and; iii) decipher the impact of signaling cues altering these processes in stem cell homeostasis and during differentiation. Ultimately, our plan includes iv) developing novel tools to track chromatin states to monitor locus-specific chromatin plasticity over time across multiple cell divisions.
Approach
We employ both established and novel pulse-chase approaches to define and monitor chromatin composition at the local or global level. We utilize genomics (SCAR/ChOR-seq) and proteomics (iPOND, APEX) in combination with fast-acting genetic perturbations aiming to reveal the multilayered chronology of chromatin plasticity. Our studies use fission yeast (Schizosaccharomyces pombe) and mouse embryonic stem cell cultures to identify both common and unique principles of chromatin state propagation in eukaryotes.
Impact
Maintaining chromatin states is essential for preserving cellular identity and is often misregulated in many diseases, particularly in cancer. Yet, the temporal order of events leading to disease remains poorly understood due to a lack of appropriate tools to track chromatin state changes over time. Therefore, to understand the underlying principles of disease formation, we aim to track the spatiotemporal changes across cell divisions. This will enable us to define cell cycle stages that are susceptible to modulate epigenome plasticity and cell identity.