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The contribution of TET proteins during global DNA demethylation in epigenetic reprogramming and pluripotency induction

In mammalian cells, the genetic information encoded in DNA is coated by chemical marks called methylation, often to turn off gene messages. Widespread removal of these marks is critical in embryonic and germ cells to reset the developmental life cycle clock. Similarly, experimental methods to revert adult cells to embryonic-like cells, called induced pluripotent stem cells (iPSCs), involve global loss of DNA methylation in the final stages, but which genes absolutely depend on that and why many others do not is not understood. Here, we study a class of proteins called TET that remove DNA methylation. Using mouse systems, we examine how cells lose DNA methylation and change in identity in the final steps in becoming iPSCs. In these cells, we use new sequencing technologies to understand the process by which DNA regions open, how DNA-associated proteins called histones change in status to reflect gene activation or silencing and how these changes coordinate with the DNA binding and activities of TET proteins.

Date:1 Sep 2021 →  Today
Keywords:Neurulation, Epigenetics, Chromatin accessibility, DNA methylation, Cell fate, Embryonic stem cells
Disciplines:Stem cell biology, Developmental biology, Developmental neuroscience, Epigenetics
Project type:PhD project