Identification and Characterization of Klf4 Functional Domains in Somatic Cell Reprogramming
- Author(s): Schmidt, Ryan
- Advisor(s): Martin, Kelsey C;
- Plath, Kathrin
- et al.
Somatic cell reprogramming refers to the conversion of a differentiated cell with restricted developmental potential to a pluripotent cell through the collective action of defined factors. This method of resetting the epigenome to an embryonic-like state has tremendous medical implications since these cells can subsequently be converted into any cell type of the body for use in regenerative therapies. The reprogramming process is most often initiated by the expression of three transcription factors - Oct4, Sox2, and Klf4 - in a target cell. This work aims to better understand the mechanism of reprogramming by mapping functional domains in the Klf4 protein that are required for the induction of pluripotency. Within these important regions of Klf4, we characterize specific contact sites with DNA and cofactor proteins that determine its reprogramming activity. Finally, to further understand the properties within the DNA binding domain of Klf4 that enable its reprogramming activity, we determine the in vitro binding preferences of DNA binding domains within the Klf family and demonstrate the molecular basis of their functional divergence in somatic cell reprogramming.