Project description:This SuperSeries is composed of the following subset Series: GSE29992: Genome-wide profiling of E12.5 cardiomyocytes RNA expression in both hetozygeous control and mutant GSE29994: ChIP-seq of Ezh2 and H3K27me3 in E12.5 heart apex Refer to individual Series
Project description:Congenital heart disease is among the most frequent major birth defects. Epigenetic marks are crucial for organogenesis, but their role in heart development is poorly understood. Polycomb Repressive Complex 2 (PRC2) trimethylates histone H3 at lysine 27, establishing H3K27me3 repressive epigenetic marks that promote tissue-specific differentiation by silencing ectopic gene programs. We studied the function of the catalytic subunit of PRC2, EZH2, in murine heart development. Early EZH2 inactivation by Nkx2-5Cre caused lethal congenital heart malformations, but slightly later EZH2 inactivation by cTNT-Cre did not. To study how the cardiomyocytes gene expression program is properly established in the early heart development, we combined the technologies of RNA sequencing and chromatin immunoprecipitation sequencing to identify the functional target genes directly repressed by EZH2. Intriguingly, these were enriched for transcriptional regulators of non-cardiac expression programs, such as transcription factors that regulate neuronal (Pax6) and cardiac progenitor genes (Isl1 and Six1). EZH2 was also required to maintain spatiotemporal regulation of cardiac gene expression, as Hcn4, Mlc2a, and Bmp10 were inappropriately upregulated in ventricular RNA. Furthermore, EZH2 was required for normal cardiomyocyte proliferation, establishing H3K27me3 epigenetic marks at cell cycle inhibitors Ink4a/b and repressing their expression. Our study reveals a previously undescribed role of EZH2 in regulating heart formation and shows that perturbation of the epigenetic landscape early cardiogenesis has sustained disruptive effects at later developmental stages. 8 E12.5 heart apex were used for RNA preparation each group.
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
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from Mus musculus tissues (Heart, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
Project description:SILAC based protein correlation profiling using size exclusion of protein complexes derived from seven Mus musculus tissues (Heart, Brain, Liver, Lung, Kidney, Skeletal Muscle, Thymus)
