Protein intrinsic disorder and induced pluripotent stem cells

Abstract

Induced pluripotent stem (iPS) cells can be obtained from terminally differentiated somatic cells by overexpression of defined sets of reprogramming transcription factors. These protein sets have been called the Yamanaka factors, namely Sox2, Oct3/4 (Pou5f1), Klf4, and c-Myc, and the Thomson factors, namely Sox2, Oct3, Lin28, and Nanog. Other sets of proteins, while not essential for the formation of iPS cells, are important for improving the efficiency of the induction and still other sets of proteins are important as markers for embryonic stem cells. Structural information about most of these important proteins is very sparse. Our bioinformatics analysis herein reveals that these reprogramming factors and most of the efficiency-improving and embryonic stem cell markers are highly enriched in intrinsic disorder. As is typical for transcription factors, these proteins are modular. Specific sites for interaction with other proteins and DNA are dispersed in the long regions of intrinsic disorder. These highly dynamic interaction sites are evidently responsible for the delicate interplay among various molecules. The bioinformatics analysis given herein should facilitate the investigation of the roles and organization of these modular interaction sites, thereby helping to shed further light on the pathways that underlie the mechanism(s) by which terminally differentiated cells are converted to iPS cells.