A transcribed enhancer dictates mesendoderm specification in pluripotency
| Autor: | Ching-Chia Ting, Jasmin Kernen, Frédéric Burdet, Samir Ounzain, Damien Maison, Daniel Maric, Rudi Micheletti, Stephen L. Leib, Nathan J. Palpant, Isabelle Plaisance, Michael Alexanian, Stephen P. Jenkinson, Mark Ibberson, Mohamed Nemir, Dominic Villeneuve, Nouria Hernandez, Clayton E. Friedman, Iole Pezzuto, Thierry Pedrazzini, Marco Mina |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
animal structures Science Cellular differentiation Induced Pluripotent Stem Cells General Physics and Astronomy 610 Medicine & health Biology Article General Biochemistry Genetics and Molecular Biology Cell Line Mesoderm Mice 03 medical and health sciences Ectoderm Animals Humans Cell Lineage Epigenetics lcsh:Science Induced pluripotent stem cell Enhancer Gene Transcription factor Embryonic Stem Cells Genetics Neural Plate Multidisciplinary Gene Expression Profiling Gene Expression Regulation Developmental Cell Differentiation General Chemistry Embryonic stem cell Cell biology Gene expression profiling Enhancer Elements Genetic 030104 developmental biology embryonic structures 570 Life sciences biology lcsh:Q RNA Long Noncoding |
| Zdroj: | 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 Nature Communications, vol. 8, no. 1, pp. 1806 Nature Communications, Vol 8, Iss 1, Pp 1-19 (2017) Nature Communications |
| DOI: | 10.1038/s41467-017-01804-w |
| Popis: | 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. Long noncoding RNAs (lncRNAs) are key regulators of lineage specification during development. Here, the authors investigate remodeling of enhancers and regulation of the lncRNA transcriptome during mesendoderm specification, and identify a pluripotent stage-specific transcribed enhancer controlling adoption of the mesendodermal cell fate. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|