1. Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo

MELANIE D. WHITE, JUAN FRANCISCO ANGIOLINI, YANINA D. ALVAREZ, GURPREET KAUR, ZIQING W. ZHAO, ESTEBAN MOCSKOS, LUCIANA BRUNO, STEPHANIE BISSIERE, VALERIA LEVI, NICOLAS PLACHTA

CELL

CELL PRESS

Lugar: United States; Año: 2016 vol. 165 p. 75 - 86

0092-8674

Transcription factor (TF) binding to DNA is fundamentalfor gene regulation. However, it remains unknownhow the dynamics of TF-DNA interactionschange during cell-fate determination in vivo. Here,we use photo-activatable FCS to quantify TF-DNAbinding in single cells of developing mouse embryos.In blastocysts, the TFs Oct4 and Sox2, which controlpluripotency, bind DNA more stably in pluripotentthan in extraembryonic cells. By contrast, in thefour-cell embryo, Sox2 engages in more long-livedinteractions than does Oct4. Sox2 long-lived bindingvaries between blastomeres and is regulated byH3R26 methylation. Live-cell tracking demonstratesthat those blastomeres with more long-lived bindingcontribute more pluripotent progeny, andreducing H3R26 methylation decreases long-livedbinding, Sox2 target expression, and pluripotentcell numbers. Therefore, Sox2-DNA binding predictsmammalian cell fate as early as the four-cell stage.More generally, we reveal the dynamic repartitioningof TFs between DNA sites driven by physiologicalepigenetic changes.