Year: 2017
Type: article
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.
Source: Nature Communications
Authors: 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, Iole Pezzuto, Dominic Villeneuve, Frédéric Burdet, Mark Ibberson, Stephen L. Leib, Nathan J. Palpant, Nouria Hernandez, Samir Ounzain, Thierry Pedrazzini
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: Identification of miRNAs modulating the regenerative response of the heart in the zebrafish and the mouse, Regenerative therapy for heart disease via modulation of long noncoding RNAs, G544591541, G8105150848, Improving the outcome of bacterial meningitis: combination versus single drug adjuvant therapies, G8690818240, G8854993982
OpenAlex ID: W2769312567