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| Status |
Public on May 02, 2019 |
| Title |
Pioneering function of Isl1 in the epigenetic control of cardiomyocyte cell fate [Isl1_E8_75_RNA_seq] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Generation of widely differing and specialized cell types from a single totipotent zygote involves large-scale transcriptional changes and chromatin reorganization. Pioneer transcription factors play key roles in programming the epigenome and facilitating recruitment of additional regulatory factors during successive cell lineage specification and differentiation steps. Here we show that Isl1 acts as a pioneer factor driving cardiomyocyte lineage commitment by shaping the chromatin landscape of cardiac progenitor cells. Using an Isl1 hypomorphic mouse line which shows congenital heart defects, genome-wide profiling of Isl1 binding together with RNA- and ATAC-sequencing of cardiac progenitor cells and their derivatives, we uncover a regulatory network downstream of Isl1 that orchestrates cardiogenesis. Mechanistically, we show that Isl1 binds to compacted chromatin and woks in concert with the Brg1-Baf60c-based SWI/SNF complex to promote permissive cardiac lineage-specific alterations in the chromatin landscape not only of genes with critical functions in cardiac progenitor cells, but also of cardiomyocyte structural genes that are highly expressed when Isl1 itself is no longer present. Thus, the Isl1/Brg1-Baf60c complex plays a crucial role in orchestrating proper cardiogenesis and in establishing epigenetic memory of cardiomyocyte fate commitment.
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| Overall design |
To gain insight into the molecular mechanisms underlying Isl1 function in cardiogenesis we performed RNA-Seq from Isl1-KO embryos at E8.5 to E9.
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| Contributor(s) |
Cordero J, Gao R, Dobreva G |
| Citation(s) |
31024170 |
| |
| Submission date |
Feb 11, 2019 |
| Last update date |
Jul 22, 2019 |
| Contact name |
Gergana Dobreva |
| E-mail(s) |
Gergana.Dobreva@medma.uni-heidelberg.de
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| Organization name |
Medical Faculty Mannheim/University of Heidelberg
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| Department |
Cardiovascular Genomics and Epigenomics
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| Lab |
AG Dobreva
|
| Street address |
Ludolf-Krehl-Str. 7-11
|
| City |
Mannheim |
| State/province |
Baden Württemberg |
| ZIP/Postal code |
68167 |
| Country |
Germany |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (8)
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| This SubSeries is part of SuperSeries: |
| GSE80383 |
Pioneering function of Isl1 in the epigenetic control of cardiomyocyte cell fate |
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| Relations |
| BioProject |
PRJNA521785 |
| SRA |
SRP185578 |
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