Nuclear foundations of cellular potency (NUCLEARPOTENCY)
Nuclear foundations of cellular potency
Start date: Feb 1, 2012,
End date: Jan 31, 2018
A fundamental question in biology is to understand the mechanisms underlying cell plasticity. Such plasticity or potency is essential to form multiple cell types upon differentiation. In mammals, upon fertilization and fusion of the gametes –two highly differentiated cells- intense chromatin remodeling and epigenetic reprogramming, the reversion into an undifferentiated state, are essential to restore full developmental potency (totipotency). Subsequent development and differentiation are accompanied with progressive loss of plasticity. The transition between totipotency and the gradual loss of plasticity is thought to be regulated by yet-unknown epigenetic mechanisms.The embryonic chromatin displays unique features compared to differentiated cells, including the lack of ‘conventional’ heterochromatin. We hypothesise that the transition from a totipotent state to a differentiated one is regulated by changes in chromatin states, particularly by de novo acquisition of heterochromatin domains.This project is designed to reveal the nuclear foundations of totipotency by determining the molecular mechanisms underlying the establishment of heterochromatin and their functional role in maintaining totipotency using the mouse embryo as model.We will do this by:i)determining the functional relationship of heterochromatin and nuclear architectureii)by determining the effects of artificially inducing heterochromatin on cell potency during development andiii)by determining the mechanisms that regulate heterochromatin formation in the embryo.We anticipate that our studies will unravel fundamental mechanims on how chromatin states regulate cell potency during reprogramming. By uncovering such mechanisms, we expect to reveal new insights that will be useful to induce epigenetic reprogramming of differentiated cells. Our results will therefore lead to key contributions in the fields of stem cell, developmental biology, human reproduction, chromatin biology and epigenetics.
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