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Divergent mechanisms of EZH1 regulation of heart development and regeneration

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE97733 | GEO | 2017/07/26

SECONDARY ACCESSION(S): PRJNA382777

REPOSITORIES: GEO

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Divergent Requirements for EZH1 in Heart Development Versus Regeneration.

Project description:RATIONALE:Polycomb repressive complex 2 is a major epigenetic repressor that deposits methylation on histone H3 on lysine 27 (H3K27me) and controls differentiation and function of many cells, including cardiac myocytes. EZH1 and EZH2 are 2 alternative catalytic subunits with partial functional redundancy. The relative roles of EZH1 and EZH2 in heart development and regeneration are unknown. OBJECTIVE:We compared the roles of EZH1 versus EZH2 in heart development and neonatal heart regeneration. METHODS AND RESULTS:Heart development was normal in Ezh1-/- (Ezh1 knockout) and Ezh2f/f::cTNT-Cre (Ezh2 knockout) embryos. Ablation of both genes in Ezh1-/-::Ezh2f/f::cTNT-Cre embryos caused lethal heart malformations, including hypertrabeculation, compact myocardial hypoplasia, and ventricular septal defect. Epigenome and transcriptome profiling showed that derepressed genes were upregulated in a manner consistent with total EZH dose. In neonatal heart regeneration, Ezh1 was required, but Ezh2 was dispensable. This finding was further supported by rescue experiments: cardiac myocyte-restricted re-expression of EZH1 but not EZH2 restored neonatal heart regeneration in Ezh1 knockout. In myocardial infarction performed outside of the neonatal regenerative window, EZH1 but not EZH2 likewise improved heart function and stimulated cardiac myocyte proliferation. Mechanistically, EZH1 occupied and activated genes related to cardiac growth. CONCLUSIONS:Our work unravels divergent mechanisms of EZH1 in heart development and regeneration, which will empower efforts to overcome epigenetic barriers to heart regeneration.

| S-EPMC5527745 | biostudies-literature

Divergent mechanisms of EZH1 regulation of heart development and regeneration [RNA-Seq]

Project description:RNA-seq for DKO, E1KO, E2KO and WT E12.5 heart revealed that EZH1 and EZH2 play a partially redundant role to trimethylate histone H3 at Lys 27 (H3K27me3). Through EZH1, H3K27me3 and H3K27ac ChIP-seq and RNA-seq for P13 EZH1 and GFP overexpressing heart (AAVEzh1 and AAVGFP respectively) suffered MI at P10, we surprisingly found that EZH1 can active the expression of regenerating relevant genes by directly binding to the promoter of targeted genes and through a mechanism independent of H3K27me3 deposition. Together, we unravel a requirement but divergent mechanisms of EZH1 in heart development and regeneration

2017-07-26 | GSE97732 | GEO

Divergent mechanisms of EZH1 regulation of heart development and regeneration [ChIP-Seq]

Project description:Through EZH1, H3K27me3 and H3K27ac ChIP-seq and RNA-seq data in P13 EZH1 and GFP overexpressing heart (AAVEzh1 and AAVGFP respectively) suffered MI at P10, we surprisingly found that EZH1 can active the expression of regenerating relevant genes by directly binding to the promoter of targeted genes and through a mechanism independent of H3K27me3 deposition.

2017-07-26 | GSE97731 | GEO

Divergent mechanisms of EZH1 regulation of heart development and regeneration

Project description:Divergent mechanisms of EZH1 regulation of heart development and regeneration

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Chromatin accessibility landscapes revealed the subgenome-divergent regulation networks during wheat grain development.

Project description:This SuperSeries is composed of the SubSeries listed below.

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Project description:This SuperSeries is composed of the SubSeries listed below.

2023-05-26 | GSE216649 | GEO

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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