CanCell seminar with Effie Apostolou: "Constructing 4D molecular roadmaps of cell fate decisions

"Every time that a cell divides "decides" whether it will maintain its identity (self-renewal) or give rise to a new cell type, e.g. during differentiation, reprogramming or transformation. In my group, we study the interplay between transcription and epigenetic factors with 3D chromatin topology and their roles in cell fate decisions. In this talk, I will mostly focus on the mechanisms that ensure self-renewal, and specifically how cell type-defining features that are drastically perturbed during mitosis, are faithfully reestablished in the daughter cells upon G1 entry. We recently characterized at a genome-wide scale the dynamic transcriptional and architectural resetting of mouse pluripotent stem cells (PSCs) upon mitotic exit. We captured distinct waves of transcriptional reactivation with rapid induction of stem cell genes and transient activation of lineage-specific genes. Topological reorganization at different hierarchical levels also occurred in an asynchronous manner and showed partial coordination with transcriptional resetting. Globally, rapid transcriptional and architectural resetting associated with mitotic retention of H3K27 acetylation, supporting a bookmarking function. Indeed, mitotic depletion of H3K27ac impaired the early reactivation of bookmarked, stem cell-associated genes. However, 3D chromatin reorganization remained largely unaffected, suggesting these processes are driven by distinct forces upon mitotic exit. I will discuss the impact of this study and critical open questions in the field."