Mitotic bookmarking by transcription factors as a mechanism of transcriptional memory

Cells that are the building blocks of the organism come in different forms and functions. Stem cells are a unique type of cells, because of their ability to change (differentiate) or maintain their state. Because of this ability to differentiate into any type of cell, stem cells are on the frontiers of regenerative medicine, which is aimed to restore damaged cells, tissues or organs. The cell division (mitosis) poses a challenge for cell identity. During mitosis, the DNA is condensed into characteristic mitotic chromosomes, the nuclear membrane, separating DNA from rest of the cell, is fragmented, and the gene expression ceases. How then cells memorized which genes were expressed, to continue their expression after mitosis? The mitotic memory has been proposed as a mechanism for the maintenance of cell identity after mitosis. One arm of this mechanism, called bookmarking, is the binding of transcription factors (proteins regulating gene expression), to mitotic DNA. This project aims to establish the molecular mechanisms of mitotic bookmarking in mouse embryonic stem cells. Using methods, such as gene editing, genomics, and imaging, I will solve how stem cells maintain their identity after countless number of cell division.