Spatiotemporal investigation of the MuvB/DREAM pathway in cell cycle gene expression programs

The cell cycle is the fundamental biological process where the cell coordinates chromosome replication and segregation with cell growth and division. Cell cycle exit controls cell proliferation and is crucial for development, tissue regeneration, and tumour biology. Cell cycle progression is promoted by the cyclins, which activate the cyclin-dependent kinases and are regulated at the transcriptional level. A key regulator of cellular proliferation and cell cycle exit is the MuvB complex, a bifunctional transcriptional regulator which represses cyclin genes during cell cycle exit (i.e.DREAM complex), and switches to an activator during cell proliferation. Although the MuvB pathway is crucial for controlling cell proliferation and its dual function in transcription is intriguing, we do not know how these processes work at the molecular level. To increase our knowledge into the latter, we aim to investigate (i) the mechanism(s) of transcriptional regulation by the MuvB complexes (ii) the interplay between MuvB and its associated factors/enzymes (iii) the MuvB switch from repressor to an activator. This will propel our understanding of how a dual function transcriptional regulator can switch from a repressor to an activator to control cellular proliferation, thereby gaining insights into how cell cycle dependant transcription fine tune the cell cycle.