“Epigenetic reprogramming encompasses changes in nuclear architecture and epigenetic modifications that lead to a shift in gene expression profile and cell identity.”
Development of any organism starts with a totipotent cell (zygote). Through series of cell divisions and differentiation processes this cell will give rise to the whole organism containing hundreds of specialised cells. While the cells at the onset of development have the capacity to generate all cell types (ie are toti-or pluripotent), this developmental capacity is progressively lost as the cells undertake cell fate decisions. At the molecular level, the memory of these events is laid down in a complex layer of epigenetic modifications at both the DNA and the chromatin level.
The main research focus of our laboratory is trying to understand molecular processes that underlie global erasure of epigenetic information. As in vitro cellular reprogramming systems are notoriously inefficient and heterogeneous in outcome, we focus on the epigenetic reprogramming events that occur naturally in vivo during mouse development (in the mouse zygote and in the early mouse germ cells). We are particularly interested in:
1) the erasure and dynamics of DNA modifications during these processes and
2) the chromatin assembly/disassembly and underlying histone dynamics.
As epigenetic reprogramming plays a pivotal role in the dedifferentiation and the reversal of cell fate decisions, investigation of molecular pathways underlying such processes provides direct mechanistic links to regeneration and cancer.
Figure 1: Overview of major epigenetic changes during mouse development.
Figure 2: Interplay between chromatin changes and hallmarks of DNA repair during germline epigenetic reprogramming.
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