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| Status |
Public on Sep 17, 2019 |
| Title |
H3K27me3 deposition over sarcomeric and cytoskeletal promoters is required for cardiomyocyte cytokinesis and wound invasion during zebrafish heart regeneration [RNA-seq] |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
We identify the global transcriptional changes that occur between homeostatic and proliferative cardiomyocytes in the zebrafish heart and uncover an essential role for H3K27me3 deposition in facilitating successful myocardial regeneration. Specifically, we learned that cardiomyocyte proliferation is accompanied by downregulation of sarcomeric and cytoskeletal components and upregulation of the polycomb methylase Ezh2. Using ChIPseq, we demonstrate that this transcriptional repression is associated with deposition of new H3K27me3 modifications over the promoters. Using new genetic zebrafish lines that allow for inducible and cardiomyocyte-specific expression of a mutant form of histone 3 that is unable to be tri-methylated on lysine 27 (H3.3K27M), we discovered that addition of H3K27me3 marks is essential for cardiac regeneration in vivo. Earlier in the regenerative window, we found that H3.3K27M–expressing wound edge cardiomyocytes aberrantly maintain homeostatic levels of sarcomeric and actomyosin gene expression and show significant retention of sarcomere structure. While DNA replication occurs normally in these H3.3K27M cardiomyocytes, we observed significant increases in cardiomyocyte nucleation, a phenotype indicative of cytokinesis failures. In addition, nuclear density at the wound edge increases as new cardiomyocytes fail to colonize the injured area. Together, our study reveals that production of new cardiomyocytes and their infiltration into the injured region relies on H3K27me3-mediated sarcomeric and actomyosin cytoskeletal gene repression.
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| Overall design |
Transcriptional profiling (RNA-seq) of regenerting versus uninjured FACS-purified cardiomyocytes from zebrafish ventricle apexes in triplicates
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| Contributor(s) |
Ben-Yair R, Butty V, Boyer LA, Goren A, Busby M, Burns CG, Burns CE |
| Citation(s) |
31427288 |
| Submission date |
Mar 22, 2017 |
| Last update date |
Sep 20, 2019 |
| Contact name |
Raz Ben-Yair |
| E-mail(s) |
razbe@weizmann.ac.il
|
| Phone |
6177553081
|
| Organization name |
MGH
|
| Department |
CVRC
|
| Lab |
Caroline Burns
|
| Street address |
13th st.
|
| City |
Charlestown, MA |
| State/province |
MA |
| ZIP/Postal code |
02129 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL14875 |
Illumina HiSeq 2000 (Danio rerio) |
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| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE96930 |
H3K27me3-mediated silencing of structural genes is required for zebrafish heart regeneration |
|
| Relations |
| BioProject |
PRJNA380129 |
| SRA |
SRP102311 |
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