Combinatorial chromatin dynamics foster accurate cardiopharyngeal fate choices

Abstract
Data availability
Article and author information
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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.

The following data sets were generated

(2019) Genome-wide maps of chromatin accessibility governing the transition from founder cells to distinct fate-restricted cardiopharyngeal precursors
NCBI Gene Expression Omnibus, GSE126691.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE126691

The following previously published data sets were used

1. Wang W
2. Niu X
3. Stuart T
4. Jullian E
5. Mauck WM
6. Kelly RG
7. Satija R
8. Christiaen L
(2019) A single cell transcriptional roadmap for cardiopharyngeal fate diversification
NCBI Gene Expression Omnibus, GSE99846.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE99846
1. Christiaen L
2. Davidson B
3. Kawashima T
4. Powell W
5. Nolla H
6. Vranizan K
7. Levine M
(2008) Transcription profiling of B7.5 lineage cells in the tunicate Ciona intestinalis to study cardiac cell migration
ArrayExpress, E-MEXP-1478.

https://www.ebi.ac.uk/arrayexpress/experiments/E-MEXP-1478/
1. Razy-Krajka F
2. Lam K
3. Wang W
4. Stolfi A
5. Joly M
6. Bonneau R
7. Christiaen L
(2014) Collier/OLF/EBF-dependent transcriptional dynamics control muscle specification from cardiopharyngeal progenitors
NCBI Gene Expression Omnibus, GSE54746.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54746

Article and author information

Author details

Claudia Racioppi

Center for Developmental Genetics, Department of Biology, New York University, New York, United States

For correspondence
cr1636@nyu.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8117-1124
Keira A Wiechecki

Center for Developmental Genetics, Department of Biology, New York University, New York, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0572-6284
Lionel Christiaen

Center for Developmental Genetics, Department of Biology, New York University, New York, United States

For correspondence
lc121@nyu.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5930-5667

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

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.