Project description
Insight into the importance of transcriptional inactivation during cell division
Cells undergoing mitotic division cease most transcriptional activity. However, it is not clear whether this is necessary for accurate chromosome segregation or just a consequence of cell division. The EU-funded ChromoSilence project aims to uncover the importance of mitotic transcriptional inactivation (MTI) in nuclear division. To achieve this, researchers will employ acute perturbation approaches that will allow them to study cellular process with unprecedented temporal resolution. The project is expected to unveil the mechanisms and players that drive MTI and determine its impact on developmental processes and cell specification.
Objective
Coordination between major cellular functions, such as transcription and proliferation, is critical to ensure cell survival. It has long been recognised that while in mitosis, cells switch-off most of their transcriptional activity. While Mitotic Transcriptional Inactivation (MTI) is entrenched as a dogma in cell biology, its functional consequences have been difficult to pin down, as manipulating MTI in the context of a developing organism has been difficult until now. My lab has pioneered the use of acute perturbation approaches to dissect cellular process with unprecedented temporal resolution, which hold the prospect of surpassing current limitations on the identification and manipulation of multiple MTI layers. Using these novel approaches, ChromoSilence aims to test the hypothesis that MTI is a vital process for proper genome partitioning and transcriptional control. We will focus our analysis on chromosome-based events, that we propose as key contributors for MTI regulation, and test how classic chromosome assembly factors impact on mitotic transcriptional shutdown. In parallel, and supported by strong preliminary observations for a putative candidate, we will identify and reveal the function of novel players involved in chromosome-based mechanisms to drive MTI. New knowledge on the MTI mechanisms will be used to develop tools to uncover the role of this transcriptional shutdown in the fidelity of nuclear division and thereby identify novel routes to maintenance of genome stability. We will additionally uncover how the transcriptional silencing during mitosis may impact on maintenance of transcriptional programs in various developmental contexts. Collectively, ChromoSilence will reveal that MTI is not a by-product of passage through mitosis but instead an essential process for accurate chromosome segregation, maintenance of cell identity and organism development.
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
1067-001 LISBOA
Portugal