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Mitotic Bookmarking, Stem Cells and early Development

Periodic Reporting for period 2 - BinD (Mitotic Bookmarking, Stem Cells and early Development)

Reporting period: 2020-03-01 to 2021-08-31

The BinD project addresses a largely overlooked question in gene regulation: how do transcription factors convey gene regulatory information during mitosis. This question is of major importance should we want to understand how proliferative processes impact with basic aspects of gene regulation. In this project, we specifically aim at discovering mitotic bookmarking factors (i.e. transcription factors that remain active during mitosis) and dissect their mechanisms of action in the context of early mouse embryogenesis and early embryo-derived stem cells. The knowledge that will be produced will foster our control over stem cell populations and reprogramming approaches, central for regenerative medicine applications, as well as inform new hypotheses beyond stem cell biology, particularly in the field of cancer biology where proliferation is of paramount importance.
Since the start of BinD we have discovered several new mitotic bookmarking factors with a role in embryonic stem cell self-renewal. We have also proposed a new mechanism of action centred on functional interactions between mitotic bookmarking factors and the nucleosomes, the building blocks of the chromatin.
We expect to discover several other bookmarking factors, especially in other stem cell populations derived from early embryos, and study their biological function in vivo. We will also tease apart the specific contribution of mitotic bookmarking factors compared to more canonical mechanisms of epigenetic inheritance based on chromatin modifications.
Green: TF Esrrb Red: ki67 protein localising at the periphery of each mitotic chromosome