Genomics

Dataset Information

0

Suppression of canonical TGF-β signaling enables GATA4 to interact with H3K27me3 demethylase JMJD3 to promote cardiomyogenesis


ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE145290 | GEO | 2021/02/13

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

| PRJNA606600 | ENA
2016-12-15 | GSE85623 | GEO
2012-08-03 | GSE27445 | GEO
2022-09-14 | GSE193908 | GEO
2022-09-14 | GSE193791 | GEO
2022-09-14 | GSE193789 | GEO
2022-09-14 | GSE193788 | GEO
2022-09-14 | GSE193809 | GEO
2021-03-26 | E-MTAB-9986 | biostudies-arrayexpress
2011-12-30 | E-MTAB-825 | biostudies-arrayexpress