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

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. I...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mocskos, Esteban Eduardo, Bruno, Luciana, Levi, Valeria
Publicado:	2016
Materias:	DNA octamer transcription factor 4 transcription factor Sox2 Card11 protein, mouse caspase recruitment domain signaling protein green fluorescent protein histone 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 Down-Regulation Embryo, Mammalian Gene Expression Regulation, Developmental Green Fluorescent Proteins Histones Kinetics Methylation Mice Octamer Transcription Factor-3 SOXB1 Transcription Factors Spectrometry, Fluorescence
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00928674_v165_n1_p75_White http://hdl.handle.net/20.500.12110/paper_00928674_v165_n1_p75_White
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00928674_v165_n1_p75_White
record_format	dspace
spelling	paper:paper_00928674_v165_n1_p75_White2023-06-08T15:08:27Z Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo Mocskos, Esteban Eduardo Bruno, Luciana Levi, Valeria 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 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. Fil:Mocskos, E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Bruno, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Levi, V. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00928674_v165_n1_p75_White http://hdl.handle.net/20.500.12110/paper_00928674_v165_n1_p75_White
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Mocskos, Esteban Eduardo Bruno, Luciana Levi, Valeria Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo
topic_facet	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
description	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.
author	Mocskos, Esteban Eduardo Bruno, Luciana Levi, Valeria
author_facet	Mocskos, Esteban Eduardo Bruno, Luciana Levi, Valeria
author_sort	Mocskos, Esteban Eduardo
title	Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo
title_short	Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo
title_full	Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo
title_fullStr	Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo
title_full_unstemmed	Long-Lived Binding of Sox2 to DNA Predicts Cell Fate in the Four-Cell Mouse Embryo
title_sort	long-lived binding of sox2 to dna predicts cell fate in the four-cell mouse embryo
publishDate	2016
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00928674_v165_n1_p75_White http://hdl.handle.net/20.500.12110/paper_00928674_v165_n1_p75_White
work_keys_str_mv	AT mocskosestebaneduardo longlivedbindingofsox2todnapredictscellfateinthefourcellmouseembryo AT brunoluciana longlivedbindingofsox2todnapredictscellfateinthefourcellmouseembryo AT levivaleria longlivedbindingofsox2todnapredictscellfateinthefourcellmouseembryo
_version_	1768544218052034560

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

Ejemplares similares