First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor

• DOI: 10.1073/pnas.1706907114
• Publication Date: 2017-09-02T01:00:22Z
• Authors: James D. Moody; Shiri Levy; Julie Mathieu; Yalan Xing; Woojin Kim; Cheng Dong; Wolfram Tempel; Aaron M. Robitaille; Luke T. Dang; Amy Ferreccio; Damien Detraux; Sonia Sidhu; Licheng Zhu; Lauren Carter; Chao Xu; Cristina Valensisi; Yuliang Wang; R. David Hawkins; Jinrong Min; Randall T. Moon; Stuart H. Orkin; David Baker; Hannele Ruohola-B...
• Keywords: Histones; 0301 basic medicine; 03 medical and health sciences; Human Embryonic Stem Cells; Polycomb Repressive Complex 2; Humans; Computer Simulation; Methylation

Significance We describe an approach to blocking protein–protein interactions in living cells and use it to probe the earliest stages of epigenetic regulation in stem cell differentiation. We describe a computationally designed protein that tightly binds EED and disrupts PRC2 function in both cancer and stem cells. Expression of the binder at different stem cell stages identifies the first critical repressive H3K27me3 mark in embryonic development.