Alexanian, Michael; Maric, Daniel; Jenkinson, Stephen Philip; Mina, Marco; Friedman, Clayton E.; Ting, Ching-Chia; Micheletti, Rudi; Plaisance, Isabelle; Nemir, Mohamed; Maison, Damien; Kernen, Jasmin; Pezzuto, Iole; Villeneuve, Dominic; Burdet, Frédéric; Ibberson, Mark; Leib, Stephen; Palpant, Nathan J.; Hernandez, Nouria; Ounzain, Samir and Pedrazzini, Thierry (2017). A transcribed enhancer dictates mesendoderm specification in pluripotency. Nature communications, 8(1), p. 1806. Nature Publishing Group 10.1038/s41467-017-01804-w
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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
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases 04 Faculty of Medicine > Service Sector > Institute for Infectious Diseases > Research |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Jenkinson, Stephen Philip, Leib, Stephen |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2041-1723 |
Publisher: |
Nature Publishing Group |
Funders: |
[4] Swiss National Science Foundation |
Language: |
English |
Submitter: |
Stephen Leib |
Date Deposited: |
22 Feb 2018 14:41 |
Last Modified: |
05 Dec 2022 15:08 |
Publisher DOI: |
10.1038/s41467-017-01804-w |
PubMed ID: |
29180618 |
BORIS DOI: |
10.7892/boris.107446 |
URI: |
https://boris.unibe.ch/id/eprint/107446 |
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