A transcribed enhancer dictates mesendoderm specification in pluripotency

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 and 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:

25 Feb 2018 02:21

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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