Combinatorial chromatin dynamics foster accurate cardiopharyngeal fate choices
- New York University, United States
Abstract
During embryogenesis, chromatin accessibility profiles control lineage-specific gene expression by modulating transcription, thus impacting multipotent progenitor states and subsequent fate choices. Subsets of cardiac and pharyngeal/head muscles share a common origin in the cardiopharyngeal mesoderm, but the chromatin landscapes that govern multipotent progenitors competence and early fate choices remain largely elusive. Here, we leveraged the simplicity of the chordate model Ciona to profile chromatin accessibility through stereotyped transitions from naive Mesp+ mesoderm to distinct fate-restricted heart and pharyngeal muscle precursors. An FGF-Foxf pathway acts in multipotent progenitors to establish cardiopharyngeal-specific patterns of accessibility, which govern later heart vs. pharyngeal muscle-specific expression profiles, demonstrating extensive spatiotemporal decoupling between early cardiopharyngeal enhancer accessibility and late cell-type-specific activity. We found that multiple cis-regulatory elements, with distinct chromatin accessibility profiles and motif compositions, are required to activate Ebf and Tbx1/10, two key determinants of cardiopharyngeal fate choices. We propose that these 'combined enhancers' foster spatially and temporally accurate fate choices, by increasing the repertoire of regulatory inputs that control gene expression, through either accessibility and/or activity.
Data availability
All sequencing data were deposited on GEO with accession GSE126691.
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A single cell transcriptional roadmap for cardiopharyngeal fate diversificationNCBI Gene Expression Omnibus, GSE99846.
Article and author information
Author details
Funding
European Molecular Biology Organization (Long Term Fellowship)
- Claudia Racioppi
National Heart, Lung, and Blood Institute (R01 HL108643)
- Lionel Christiaen
Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01 HD096770)
- Lionel Christiaen
Leducq Foundation (15CVD01)
- Lionel Christiaen
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Racioppi et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Combinatorial chromatin dynamics foster accurate cardiopharyngeal fate choices
eLife 8:e49921.
https://doi.org/10.7554/eLife.49921
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