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A transcribed enhancer dictates mesendoderm specification in pluripotency

Author

Listed:
  • Michael Alexanian

    (University of Lausanne Medical School)

  • Daniel Maric

    (University of Lausanne Medical School)

  • Stephen P. Jenkinson

    (University of Bern)

  • Marco Mina

    (University of Lausanne
    Swiss Institute of Bioinformatics)

  • Clayton E. Friedman

    (University of Queensland)

  • Ching-Chia Ting

    (University of Lausanne Medical School)

  • Rudi Micheletti

    (University of Lausanne Medical School)

  • Isabelle Plaisance

    (University of Lausanne Medical School)

  • Mohamed Nemir

    (University of Lausanne Medical School)

  • Damien Maison

    (University of Lausanne Medical School)

  • Jasmin Kernen

    (University of Bern)

  • Iole Pezzuto

    (University of Lausanne Medical School)

  • Dominic Villeneuve

    (University of Lausanne)

  • Frédéric Burdet

    (Swiss Institute of Bioinformatics)

  • Mark Ibberson

    (Swiss Institute of Bioinformatics)

  • Stephen L. Leib

    (University of Bern)

  • Nathan J. Palpant

    (University of Queensland)

  • Nouria Hernandez

    (University of Lausanne)

  • Samir Ounzain

    (University of Lausanne Medical School)

  • Thierry Pedrazzini

    (University of Lausanne Medical School)

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.

Suggested Citation

  • Michael Alexanian & Daniel Maric & Stephen P. Jenkinson & Marco Mina & Clayton E. Friedman & Ching-Chia Ting & Rudi Micheletti & Isabelle Plaisance & Mohamed Nemir & Damien Maison & Jasmin Kernen & Io, 2017. "A transcribed enhancer dictates mesendoderm specification in pluripotency," Nature Communications, Nature, vol. 8(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01804-w
    DOI: 10.1038/s41467-017-01804-w
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