CENTRO DE SIMULACION COMPUTACIONAL PARA APLICACIONES TECNOLOGICAS
Unidad Ejecutora - UE
Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo
MELAMIE D. WHITE; GURPREET KAUR; LUCIANA BRUNO; NICOLAS PLACHTA; YANINA ALVAREZ; ESTEBAN E. MOCSKOS; YANINA ALVAREZ; VALERIA LEVI; ESTEBAN E. MOCSKOS; VALERIA LEVI; JUAN FRANCISCO ANGIOLINI; ZIQING W. ZHAO; STEPHANIE BISSIERE; JUAN FRANCISCO ANGIOLINI; ZIQING W. ZHAO; STEPHANIE BISSIERE; MELAMIE D. WHITE; GURPREET KAUR; LUCIANA BRUNO; NICOLAS PLACHTA
Lugar: United States; Año: 2016 vol. 165 p. 75 - 75
Transcription factor (TF) binding to DNA is fundamental for gene regulation.However, it remains unknown how the dynamics of TF?DNA interactions change during cell fate determination in vivo. Here, we use photo-activatable FCS to quantify TF?DNA binding in single cells of developing mouse embryos.In blastocysts, the TFs Oct4 and Sox2, which control pluripotency, bind DNA more stably in pluripotent than extraembryonic cells. By contrast, in the 4-cell embryo, Sox2 engages in more long-lived interactions than Oct4. Sox2 long-lived binding varies between blastomeres and is regulated by H3R26 methylation. Live-cell tracking demonstrates that those blastomeres with more long-lived binding contribute more pluripotent progeny, and reducing H3R26 methylation decreases long-lived binding, Sox2 target expression andpluripotent cell numbers. Therefore, Sox2?DNA binding predicts mammalian cell fate as early as the 4-cell stage. More generally, we reveal the dynamic repartitioning of TFs between DNA sites driven by physiological epigenetic changes.