Projet : DNA replication origins and cell identity

We found that the positions of DNA replication origins is associated with the organization of chromosomal domains, and that this positioning may define the cell fate determination in a process linked to development. We provided a first evidence for this model several years ago during Xenopus early development. We then demonstrated a correlation between the activation of transcription and the positioning of some DNA replication origins (Danis et al, 2004).

We also spotted the coupling between DNA replication and gene expression during the differentiation of pluripotent teratocarcinoma cells into neural cells (Fisher et al, 2003; Gregoire et al, 2006), and observed a similar link during  C. Elegans development (Rodriguez et al, 2017).

We also showed that an extensive reprogramming of DNA replication origin organization occurs when a nucleus from a differentiated cell is exposed to an embryonic context (Lemaitre et al, 2005 ; Ganier et al, 2011) in a   topoisomerase II-dependent process (Cuvier et al, 2008). This process parallels the transcriptional reprogramming of differentiated nuclei (Ganier et al, 2011).More recently, we showed genome-wide replication origin reprogramming during development.