White, M.D.; Angiolini, J.F.; Alvarez, Y.D.; Kaur, G.; Zhao, Z.W.; Mocskos, E.; Bruno, L.; Bissiere, S.; Levi, V.; Plachta, N. "Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo" (2016) Cell. 165(1):75-87
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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 in extraembryonic cells. By contrast, in the four-cell embryo, Sox2 engages in more long-lived interactions than does 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, and pluripotent cell numbers. Therefore, Sox2-DNA binding predicts mammalian cell fate as early as the four-cell stage. More generally, we reveal the dynamic repartitioning of TFs between DNA sites driven by physiological epigenetic changes. Video Abstract. © 2016 Elsevier Inc.


Documento: Artículo
Título:Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo
Autor:White, M.D.; Angiolini, J.F.; Alvarez, Y.D.; Kaur, G.; Zhao, Z.W.; Mocskos, E.; Bruno, L.; Bissiere, S.; Levi, V.; Plachta, N.
Filiación:Institute of Molecular and Cell Biology, A STAR, 61 Biopolis Drive, Singapore, 138673, Singapore
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, CONICET, Buenos Aires, C1428EHA, Argentina
Palabras clave:DNA; octamer transcription factor 4; transcription factor Sox2; Card11 protein, mouse; caspase recruitment domain signaling protein; DNA; green fluorescent protein; histone; octamer transcription factor 4; Pou5f1 protein, mouse; Sox2 protein, mouse; transcription factor Sox; animal experiment; Article; blastocyst; cell fate; cell tracking; controlled study; DNA binding; embryo; epigenetics; fluorescence correlation spectroscopy; mammal cell; mouse; nonhuman; priority journal; protein expression; protein methylation; protein-bound fraction; animal; diffusion; down regulation; gene expression regulation; kinetics; mammalian embryo; metabolism; methylation; spectrofluorometry; Animals; Blastocyst; CARD Signaling Adaptor Proteins; Diffusion; DNA; Down-Regulation; Embryo, Mammalian; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Histones; Kinetics; Methylation; Mice; Octamer Transcription Factor-3; SOXB1 Transcription Factors; Spectrometry, Fluorescence
Página de inicio:75
Página de fin:87
Título revista:Cell
Título revista abreviado:Cell
CAS:DNA, 9007-49-2; histone, 9062-68-4; CARD Signaling Adaptor Proteins; Card11 protein, mouse; DNA; Green Fluorescent Proteins; Histones; Octamer Transcription Factor-3; Pou5f1 protein, mouse; Sox2 protein, mouse; SOXB1 Transcription Factors


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---------- APA ----------
White, M.D., Angiolini, J.F., Alvarez, Y.D., Kaur, G., Zhao, Z.W., Mocskos, E., Bruno, L.,..., Plachta, N. (2016) . Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo. Cell, 165(1), 75-87.
---------- CHICAGO ----------
White, M.D., Angiolini, J.F., Alvarez, Y.D., Kaur, G., Zhao, Z.W., Mocskos, E., et al. "Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo" . Cell 165, no. 1 (2016) : 75-87.
---------- MLA ----------
White, M.D., Angiolini, J.F., Alvarez, Y.D., Kaur, G., Zhao, Z.W., Mocskos, E., et al. "Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo" . Cell, vol. 165, no. 1, 2016, pp. 75-87.
---------- VANCOUVER ----------
White, M.D., Angiolini, J.F., Alvarez, Y.D., Kaur, G., Zhao, Z.W., Mocskos, E., et al. Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo. Cell. 2016;165(1):75-87.