“Epigenetic reprogramming encompasses changes in nuclear architecture and epigenetic modifications that eventually lead to a shift in gene expression profile”
At the molecular level reprogramming involves the erasure of epigenetic marks including DNA methylation and histone modifications. Our lab uses in vivo models to elucidate molecular mechanisms underlying naturally occurring reprogramming events. The knowledge gained allows us to design in vitro experimental systems and to use biochemical approaches to investigate further molecular details.
We study reprogramming events both in the developing mouse germ line and in the mouse zygote. The former involves both genomewide DNA demethylation and chromatin remodelling, whereas reprogramming the zygote involves genome wide DNA demethylation affecting only the paternal genome a few hours after fertilisation.
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.
Amouroux R, Nashun B, Shirane K, Nakagawa S, Hill PW, D’Souza Z, Nakayama M, Matsuda M, Turp A, Ndjetehe E, Encheva V, Kudo NR, Koseki H, Sasaki H, Hajkova P. (2016) De novo DNA methylation drives 5hmC accumulation in mouse zygotes. Nat Cell Biol. [Epub ahead of print]
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Hajkova, P., Ancelin, K., Waldmann, T., Lacoste, N., Lange, U. C., Cesari, F., Lee, C., Almouzni, G., Schneider, R., & Surani, M. A. (2008). Chromatin dynamics during epigenetic reprogramming in the mouse germ line. Nature, 452(7189), 877–881.
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