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Trends Genet. 2012 Apr;28(4):164-74. doi: 10.1016/j.tig.2012.01.005. Epub 2012 Mar 3.

Parallel mechanisms of epigenetic reprogramming in the germline.

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Wellcome Trust/Cancer Research UK Gurdon Institute and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, CB2 1QN, UK.


Germ cells possess the extraordinary and unique capacity to give rise to a new organism and create an enduring link between all generations. To acquire this property, primordial germ cells (PGCs) transit through an unprecedented programme of sequential epigenetic events that culminates in an epigenomic basal state that is the foundation of totipotency. This process is underpinned by genome-wide DNA demethylation, which may occur through several overlapping pathways, including conversion to 5-hydroxymethylcytosine. We propose that the epigenetic programme in PGCs operates through multiple parallel mechanisms to ensure robustness at the level of individual cells while also being flexible through functional redundancy to guarantee high fidelity of the process. Gaining a better understanding of the molecular mechanisms that direct epigenetic reprogramming in PGCs will enhance our ability to manipulate epigenetic memory, cell-fate decisions and applications in regenerative medicine.

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