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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 13, 2021 |
| Title |
Suppression of canonical TGF-β signaling enables GATA4 to interact with H3K27me3 demethylase JMJD3 to promote cardiomyogenesis |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Direct reprogramming of fibroblasts into cardiomyocytes (CMs) represents a promising strategy to regenerate CMs lost after ischemic heart injury. Overexpression of GATA4, HAND2, MEF2C, TBX5, miR-1, and miR-133 (GHMT2m) along with transforming growth factor beta (TGFbeta) inhibition efficiently promotes reprogramming. However, the mechanisms by which TGFbeta; blockade promotes cardiac reprogramming remain unknown. Here, we identify interactions between the histone H3 lysine 27 trimethylation (H3K27me3), demethylase JMJD3, the SWI/SNF remodeling complex subunit BRG1, and cardiac transcription factors. Furthermore, canonical TGFbeta; signaling regulates the interaction between GATA4 and JMJD3. TGF-beta; activation impairs the ability of GATA4 to bind target genes and prevents demethylation of H3K27 at cardiac gene promoters during cardiac reprogramming. Finally, a mutation in GATA4 (V267M) exhibits reduced binding to JMJD3 and impaired cardiomyogenesis. Thus, we have identified an epigenetic mechanism wherein canonical TGFbeta; pathway activation impairs cardiac gene programming by interfering with GATA4-JMJD3 interactions.
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| Overall design |
Examination of H3K27me3 in mouse embryonic fibroblasts following induction of cardiomyocyte differentiation
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| Contributor(s) |
Riching AS, Song K |
| Citation(s) |
33359755 |
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| Submission date |
Feb 13, 2020 |
| Last update date |
Jan 02, 2024 |
| Contact name |
Etienne Danis |
| E-mail(s) |
ETIENNE.DANIS@CUANSCHUTZ.EDU
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| Organization name |
University of Colorado, Denver - Anschutz Medical Campus
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| Department |
Cancer Center
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| Street address |
13001 E 17th Pl
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| City |
AURORA |
| State/province |
CO |
| ZIP/Postal code |
80045 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA606600 |
| SRA |
SRP249394 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE145290_RAW.tar |
1.0 Gb |
(http)(custom) |
TAR (of TDF) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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