Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells.

<h4>Background</h4>The T-box transcription factor Brachyury (T) is essential for formation of the posterior mesoderm and the notochord in vertebrate embryos. Work in the frog and the zebrafish has identified some direct genomic targets of Brachyury, but little is known about Brachyury ta...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Amanda L Evans, Tiago Faial, Michael J Gilchrist, Thomas Down, Ludovic Vallier, Roger A Pedersen, Fiona C Wardle, James C Smith
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/21d739225a0f4ef7a5e245d45c078b9b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:21d739225a0f4ef7a5e245d45c078b9b
record_format	dspace
spelling	oai:doaj.org-article:21d739225a0f4ef7a5e245d45c078b9b2021-11-18T07:23:44ZGenomic targets of Brachyury (T) in differentiating mouse embryonic stem cells.1932-620310.1371/journal.pone.0033346https://doaj.org/article/21d739225a0f4ef7a5e245d45c078b9b2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22479388/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The T-box transcription factor Brachyury (T) is essential for formation of the posterior mesoderm and the notochord in vertebrate embryos. Work in the frog and the zebrafish has identified some direct genomic targets of Brachyury, but little is known about Brachyury targets in the mouse.<h4>Methodology/principal findings</h4>Here we use chromatin immunoprecipitation and mouse promoter microarrays to identify targets of Brachyury in embryoid bodies formed from differentiating mouse ES cells. The targets we identify are enriched for sequence-specific DNA binding proteins and include components of signal transduction pathways that direct cell fate in the primitive streak and tailbud of the early embryo. Expression of some of these targets, such as Axin2, Fgf8 and Wnt3a, is down regulated in Brachyury mutant embryos and we demonstrate that they are also Brachyury targets in the human. Surprisingly, we do not observe enrichment of the canonical T-domain DNA binding sequence 5'-TCACACCT-3' in the vicinity of most Brachyury target genes. Rather, we have identified an (AC)(n) repeat sequence, which is conserved in the rat but not in human, zebrafish or Xenopus. We do not understand the significance of this sequence, but speculate that it enhances transcription factor binding in the regulatory regions of Brachyury target genes in rodents.<h4>Conclusions/significance</h4>Our work identifies the genomic targets of a key regulator of mesoderm formation in the early mouse embryo, thereby providing insights into the Brachyury-driven genetic regulatory network and allowing us to compare the function of Brachyury in different species.Amanda L EvansTiago FaialMichael J GilchristThomas DownLudovic VallierRoger A PedersenFiona C WardleJames C SmithPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e33346 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amanda L Evans Tiago Faial Michael J Gilchrist Thomas Down Ludovic Vallier Roger A Pedersen Fiona C Wardle James C Smith Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells.
description	<h4>Background</h4>The T-box transcription factor Brachyury (T) is essential for formation of the posterior mesoderm and the notochord in vertebrate embryos. Work in the frog and the zebrafish has identified some direct genomic targets of Brachyury, but little is known about Brachyury targets in the mouse.<h4>Methodology/principal findings</h4>Here we use chromatin immunoprecipitation and mouse promoter microarrays to identify targets of Brachyury in embryoid bodies formed from differentiating mouse ES cells. The targets we identify are enriched for sequence-specific DNA binding proteins and include components of signal transduction pathways that direct cell fate in the primitive streak and tailbud of the early embryo. Expression of some of these targets, such as Axin2, Fgf8 and Wnt3a, is down regulated in Brachyury mutant embryos and we demonstrate that they are also Brachyury targets in the human. Surprisingly, we do not observe enrichment of the canonical T-domain DNA binding sequence 5'-TCACACCT-3' in the vicinity of most Brachyury target genes. Rather, we have identified an (AC)(n) repeat sequence, which is conserved in the rat but not in human, zebrafish or Xenopus. We do not understand the significance of this sequence, but speculate that it enhances transcription factor binding in the regulatory regions of Brachyury target genes in rodents.<h4>Conclusions/significance</h4>Our work identifies the genomic targets of a key regulator of mesoderm formation in the early mouse embryo, thereby providing insights into the Brachyury-driven genetic regulatory network and allowing us to compare the function of Brachyury in different species.
format	article
author	Amanda L Evans Tiago Faial Michael J Gilchrist Thomas Down Ludovic Vallier Roger A Pedersen Fiona C Wardle James C Smith
author_facet	Amanda L Evans Tiago Faial Michael J Gilchrist Thomas Down Ludovic Vallier Roger A Pedersen Fiona C Wardle James C Smith
author_sort	Amanda L Evans
title	Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells.
title_short	Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells.
title_full	Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells.
title_fullStr	Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells.
title_full_unstemmed	Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells.
title_sort	genomic targets of brachyury (t) in differentiating mouse embryonic stem cells.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/21d739225a0f4ef7a5e245d45c078b9b
work_keys_str_mv	AT amandalevans genomictargetsofbrachyurytindifferentiatingmouseembryonicstemcells AT tiagofaial genomictargetsofbrachyurytindifferentiatingmouseembryonicstemcells AT michaeljgilchrist genomictargetsofbrachyurytindifferentiatingmouseembryonicstemcells AT thomasdown genomictargetsofbrachyurytindifferentiatingmouseembryonicstemcells AT ludovicvallier genomictargetsofbrachyurytindifferentiatingmouseembryonicstemcells AT rogerapedersen genomictargetsofbrachyurytindifferentiatingmouseembryonicstemcells AT fionacwardle genomictargetsofbrachyurytindifferentiatingmouseembryonicstemcells AT jamescsmith genomictargetsofbrachyurytindifferentiatingmouseembryonicstemcells
_version_	1718423522085175296

Genomic targets of Brachyury (T) in differentiating mouse embryonic stem cells.

Ejemplares similares