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| Status |
Public on Sep 17, 2019 |
| Title |
H3K27me3-mediated silencing of structural genes is required for zebrafish heart regeneration |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Deciphering the genetic and epigenetic regulation of cardiomyocyte proliferation in organisms capable of robust cardiac renewal represents an attractive inroad towards regenerating the human heart. In the highly regenerative zebrafish heart, cardiomyocytes near the wound edge undergo dramatic changes in gene expression concomitant with sarcomere disassembly, loss of cell-cell adhesion, and detachment from the extracellular matrix (ECM), which leaves them poised to divide and give rise to new muscle cells that colonize the wound. Using integrated highthroughput transcriptional and chromatin analyses, we identified correlations between gene expression changes and activating H3K4me3 and/or repressive H3K27me3 dynamics8 in cardiomyocytes following injury. Within the category of downregulated genes that gain H3K27me3, transcripts encoding sarcomere and cytoskeletal components were significantly overrepresented. To investigate a functional requirement for H3K27me3-mediated gene silencing during zebrafish heart regeneration, we generated an inducible transgenic strain expressing a mutant version of histone 3, H3.3K27M, which allowed us to inhibit H3K27me3 catalysis in cardiomyocytes during the regenerative window. Hearts composed of H3.3K27M-expressing cardiomyocytes fail to regenerate with wound edge myocardium showing heightened expression of structural genes and prominent sarcomere structures. Although cell cycle re-entry was unperturbed, cytokinesis and wound invasion were significantly compromised. Collectively, our study identifies a requirement for H3K27me3-mediated silencing of structural genes during zebrafish heart regeneration and suggests that repression of similar structural components in the border zone of the infarcted human heart might improve its regenerative capacity.
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| Overall design |
Refer to individual Series
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| |
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| 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
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| Organization name |
MGH
|
| Department |
CVRC
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| Lab |
Caroline Burns
|
| Street address |
13th st.
|
| City |
Charlestown, MA |
| State/province |
MA |
| ZIP/Postal code |
02129 |
| Country |
USA |
| |
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| Platforms (2) |
| GPL14875 |
Illumina HiSeq 2000 (Danio rerio) |
| GPL20828 |
Illumina NextSeq 500 (Danio rerio) |
|
| Samples (19)
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| This SuperSeries is composed of the following SubSeries: |
| GSE96928 |
H3K27me3 deposition over sarcomeric and cytoskeletal promoters is required for cardiomyocyte cytokinesis and wound invasion during zebrafish heart regeneration [ChIP-seq] |
| GSE96929 |
H3K27me3 deposition over sarcomeric and cytoskeletal promoters is required for cardiomyocyte cytokinesis and wound invasion during zebrafish heart regeneration [RNA-seq] |
|
| Relations |
| BioProject |
PRJNA380125 |
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