Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.

Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES) cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into an...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Jonathan Göke, Marc Jung, Sarah Behrens, Lukas Chavez, Sean O'Keeffe, Bernd Timmermann, Hans Lehrach, James Adjaye, Martin Vingron
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/3bfc2751d06f42d2836d55c1cf76cd49
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3bfc2751d06f42d2836d55c1cf76cd49
record_format	dspace
spelling	oai:doaj.org-article:3bfc2751d06f42d2836d55c1cf76cd492021-11-18T05:51:42ZCombinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.1553-734X1553-735810.1371/journal.pcbi.1002304https://doaj.org/article/3bfc2751d06f42d2836d55c1cf76cd492011-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22215994/pdf/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES) cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas "gene regulatory hotspots" which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints.Jonathan GökeMarc JungSarah BehrensLukas ChavezSean O'KeeffeBernd TimmermannHans LehrachJames AdjayeMartin VingronPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 7, Iss 12, p e1002304 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Jonathan Göke Marc Jung Sarah Behrens Lukas Chavez Sean O'Keeffe Bernd Timmermann Hans Lehrach James Adjaye Martin Vingron Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.
description	Transcription factors are proteins that regulate gene expression by binding to cis-regulatory sequences such as promoters and enhancers. In embryonic stem (ES) cells, binding of the transcription factors OCT4, SOX2 and NANOG is essential to maintain the capacity of the cells to differentiate into any cell type of the developing embryo. It is known that transcription factors interact to regulate gene expression. In this study we show that combinatorial binding is strongly associated with co-localization of the transcriptional co-activator Mediator, H3K27ac and increased expression of nearby genes in embryonic stem cells. We observe that the same loci bound by Oct4, Nanog and Sox2 in ES cells frequently drive expression in early embryonic development. Comparison of mouse and human ES cells shows that less than 5% of individual binding events for OCT4, SOX2 and NANOG are shared between species. In contrast, about 15% of combinatorial binding events and even between 53% and 63% of combinatorial binding events at enhancers active in early development are conserved. Our analysis suggests that the combination of OCT4, SOX2 and NANOG binding is critical for transcription in ES cells and likely plays an important role for embryogenesis by binding at conserved early developmental enhancers. Our data suggests that the fast evolutionary rewiring of regulatory networks mainly affects individual binding events, whereas "gene regulatory hotspots" which are bound by multiple factors and active in multiple tissues throughout early development are under stronger evolutionary constraints.
format	article
author	Jonathan Göke Marc Jung Sarah Behrens Lukas Chavez Sean O'Keeffe Bernd Timmermann Hans Lehrach James Adjaye Martin Vingron
author_facet	Jonathan Göke Marc Jung Sarah Behrens Lukas Chavez Sean O'Keeffe Bernd Timmermann Hans Lehrach James Adjaye Martin Vingron
author_sort	Jonathan Göke
title	Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.
title_short	Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.
title_full	Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.
title_fullStr	Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.
title_full_unstemmed	Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.
title_sort	combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/3bfc2751d06f42d2836d55c1cf76cd49
work_keys_str_mv	AT jonathangoke combinatorialbindinginhumanandmouseembryonicstemcellsidentifiesconservedenhancersactiveinearlyembryonicdevelopment AT marcjung combinatorialbindinginhumanandmouseembryonicstemcellsidentifiesconservedenhancersactiveinearlyembryonicdevelopment AT sarahbehrens combinatorialbindinginhumanandmouseembryonicstemcellsidentifiesconservedenhancersactiveinearlyembryonicdevelopment AT lukaschavez combinatorialbindinginhumanandmouseembryonicstemcellsidentifiesconservedenhancersactiveinearlyembryonicdevelopment AT seanokeeffe combinatorialbindinginhumanandmouseembryonicstemcellsidentifiesconservedenhancersactiveinearlyembryonicdevelopment AT berndtimmermann combinatorialbindinginhumanandmouseembryonicstemcellsidentifiesconservedenhancersactiveinearlyembryonicdevelopment AT hanslehrach combinatorialbindinginhumanandmouseembryonicstemcellsidentifiesconservedenhancersactiveinearlyembryonicdevelopment AT jamesadjaye combinatorialbindinginhumanandmouseembryonicstemcellsidentifiesconservedenhancersactiveinearlyembryonicdevelopment AT martinvingron combinatorialbindinginhumanandmouseembryonicstemcellsidentifiesconservedenhancersactiveinearlyembryonicdevelopment
_version_	1718424719165751296

Combinatorial binding in human and mouse embryonic stem cells identifies conserved enhancers active in early embryonic development.

Ejemplares similares