A transcribed enhancer dictates mesendoderm specification in pluripotency.

Détails

Ressource 1Télécharger: s41467-017-01804-w.pdf (2266.19 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_BAC1BAF45834
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A transcribed enhancer dictates mesendoderm specification in pluripotency.
Périodique
Nature Communications
Auteur(s)
Alexanian M., Maric D., Jenkinson S.P., Mina M., Friedman C.E., Ting C.C., Micheletti R., Plaisance I., Nemir M., Maison D., Kernen J., Pezzuto I., Villeneuve D., Burdet F., Ibberson M., Leib S.L., Palpant N.J., Hernandez N., Ounzain S., Pedrazzini T.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
2017
Peer-reviewed
Oui
Volume
8
Numéro
1
Pages
1806
Langue
anglais
Résumé
Enhancers and long noncoding RNAs (lncRNAs) are key determinants of lineage specification during development. Here, we evaluate remodeling of the enhancer landscape and modulation of the lncRNA transcriptome during mesendoderm specification. We sort mesendodermal progenitors from differentiating embryonic stem cells (ESCs) according to Eomes expression, and find that enhancer usage is coordinated with mesendoderm-specific expression of key lineage-determining transcription factors. Many of these enhancers are associated with the expression of lncRNAs. Examination of ESC-specific enhancers interacting in three-dimensional space with mesendoderm-specifying transcription factor loci identifies MesEndoderm Transcriptional Enhancer Organizing Region (Meteor). Genetic and epigenetic manipulation of the Meteor enhancer reveal its indispensable role during mesendoderm specification and subsequent cardiogenic differentiation via transcription-independent and -dependent mechanisms. Interestingly, Meteor-deleted ESCs are epigenetically redirected towards neuroectodermal lineages. Loci, topologically associating a transcribed enhancer and its cognate protein coding gene, appear to represent therefore a class of genomic elements controlling developmental competence in pluripotency.

Pubmed
Web of science
Open Access
Oui
Création de la notice
30/11/2017 19:34
Dernière modification de la notice
20/08/2019 16:28
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