A transcribed enhancer dictates mesendoderm specification in pluripotency.

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State: Public
Version: Final published version
Serval ID
serval:BIB_BAC1BAF45834
Type
Article: article from journal or magazin.
Collection
Publications
Title
A transcribed enhancer dictates mesendoderm specification in pluripotency.
Journal
Nature Communications
Author(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
Publication state
Published
Issued date
2017
Peer-reviewed
Oui
Volume
8
Number
1
Pages
1806
Language
english
Abstract
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
Yes
Create date
30/11/2017 19:34
Last modification date
20/08/2019 16:28
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