Mus musculus
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-30076
PROVIDER: PRJNA144097 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Adult-onset diseases can be associated with in utero events, but mechanisms for this remain unknown. The polycomb histone methyltransferase, Ezh2, stabilizes transcription by depositing repressive marks during development that persist into adulthood, but its function in postnatal organ homeostasis is unknown. We show that Ezh2 stabilizes cardiac gene expression and prevents cardiac pathology by repressing the homeodomain transcription factor Six1, which functions in cardiac progenitors but is stably silenced upon cardiac differentiation. Ezh2 deletion in cardiac progenitors caused postnatal myocardial pathology and destabilized cardiac gene expression with activation of Six1-dependent skeletal muscle genes. Six1 induced cardiomyocyte hypertrophy and skeletal muscle gene expression. Furthermore, genetically reducing Six1 levels rescued the pathology of Ezh2-deficient hearts. Thus, Ezh2-mediated repression of Six1 in differentiating cardiac progenitors is essential for stable postnatal heart gene expression and homeostasis. Our results suggest that epigenetic dysregulation in embryonic progenitor cells predisposes to adult disease and dysregulated stress responses. Four samples were analyzed. RNA was obtained from ventricles from two wild type and two Ezh2-deficient hearts.
2011-12-09 | E-GEOD-34274 | biostudies-arrayexpress
Project description:Adult-onset diseases can be associated with in utero events, but mechanisms for this remain unknown. The polycomb histone methyltransferase, Ezh2, stabilizes transcription by depositing repressive marks during development that persist into adulthood, but its function in postnatal organ homeostasis is unknown. We show that Ezh2 stabilizes cardiac gene expression and prevents cardiac pathology by repressing the homeodomain transcription factor Six1, which functions in cardiac progenitors but is stably silenced upon cardiac differentiation. Ezh2 deletion in cardiac progenitors caused postnatal myocardial pathology and destabilized cardiac gene expression with activation of Six1-dependent skeletal muscle genes. Six1 induced cardiomyocyte hypertrophy and skeletal muscle gene expression. Furthermore, genetically reducing Six1 levels rescued the pathology of Ezh2-deficient hearts. Thus, Ezh2-mediated repression of Six1 in differentiating cardiac progenitors is essential for stable postnatal heart gene expression and homeostasis. Our results suggest that epigenetic dysregulation in embryonic progenitor cells predisposes to adult disease and dysregulated stress responses.
2011-12-09 | GSE34274 | GEO
Project description:Adult-onset diseases can be associated with in utero events, but mechanisms for such temporally distant dysregulation of organ function remain unknown. The polycomb histone methyltransferase, Ezh2, stabilizes transcription by depositing repressive histone marks during development that persist into adulthood, but the function of Ezh2-mediated transcriptional stability in postnatal organ homeostasis is not understood. Here, we show that Ezh2 stabilizes the postnatal cardiac gene expression program and prevents cardiac pathology, primarily by repressing the homeodomain transcription factor Six1 in differentiating cardiac progenitors. Loss of Ezh2 in embryonic cardiac progenitors, but not in differentiated cardiomyocytes, resulted in postnatal cardiac pathology, including cardiomyocyte hypertrophy and fibrosis. Loss of Ezh2 caused broad derepression of skeletal muscle genes, including the homeodomain transcription factor Six1, which is expressed in cardiac progenitors but is normally silenced upon cardiac differentiation. Many of the deregulated genes are direct Six1 targets, implying a critical requirement for stable repression of Six1 in cardiac myocytes. Indeed, upon de-repression, Six1 promotes cardiac pathology, as it was sufficient to induce cardiac hypertrophy. Furthermore, genetic reduction of Six1 levels almost completely rescued the pathology of Ezh2-deficient hearts. Thus, repression of a single transcription factor in cardiac progenitors by Ezh2 is essential for stability of the adult heart gene expression program and homeostasis. Our results suggest that epigenetic dysregulation during discrete developmental windows can predispose to adult disease and dysregulated stress responses. Global gene expression profiles of Ezh2-deficient hearts. The right ventricle and the interventricular septum of five wild type (Ezh2f/f) and four Ezh2-deficient (Ezh2f/f;Mef2cAHF::Cre) mice were analyzed.
2011-12-31 | E-GEOD-30076 | biostudies-arrayexpress
Project description:Adult-onset diseases can be associated with in utero events, but mechanisms for such temporally distant dysregulation of organ function remain unknown. The polycomb histone methyltransferase, Ezh2, stabilizes transcription by depositing repressive histone marks during development that persist into adulthood, but the function of Ezh2-mediated transcriptional stability in postnatal organ homeostasis is not understood. Here, we show that Ezh2 stabilizes the postnatal cardiac gene expression program and prevents cardiac pathology, primarily by repressing the homeodomain transcription factor Six1 in differentiating cardiac progenitors. Loss of Ezh2 in embryonic cardiac progenitors, but not in differentiated cardiomyocytes, resulted in postnatal cardiac pathology, including cardiomyocyte hypertrophy and fibrosis. Loss of Ezh2 caused broad derepression of skeletal muscle genes, including the homeodomain transcription factor Six1, which is expressed in cardiac progenitors but is normally silenced upon cardiac differentiation. Many of the deregulated genes are direct Six1 targets, implying a critical requirement for stable repression of Six1 in cardiac myocytes. Indeed, upon de-repression, Six1 promotes cardiac pathology, as it was sufficient to induce cardiac hypertrophy. Furthermore, genetic reduction of Six1 levels almost completely rescued the pathology of Ezh2-deficient hearts. Thus, repression of a single transcription factor in cardiac progenitors by Ezh2 is essential for stability of the adult heart gene expression program and homeostasis. Our results suggest that epigenetic dysregulation during discrete developmental windows can predispose to adult disease and dysregulated stress responses.
2011-12-31 | GSE30076 | GEO
Project description:EZH2 is required for gene repression in Plasmablasts
| PRJNA400234 | ENA
Project description:Epigenetic mark deposition during embryonic development contribute to postnatal homeostasis and tissue stability. Previously, we found out that Ezh2 contributes critically to the function and postnatal cell survival in bipolar cells in the retina. (Yan et al. Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1. Sci Report. doi:10.1038/srep33887) In this study, we used RNA-seq to define up- and down regulated genes in Math5CreEzh2f/f mice which express a selective deletion of Ezh2 in retinal ganglion cells (RGC). Gene expression was compared to wild type murine retinal cells.
2018-02-13 | GSE93674 | GEO
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.
2012-03-15 | E-GEOD-29992 | biostudies-arrayexpress
Project description:Epigenetic mark deposition during embryonic development contribute to postnatal homeostasis and tissue stability. Previously, we found out that Ezh2 contributes critically to the function and postnatal cell survival in bipolar cells but not in retinal ganglion cells in the retina. (Yan et al. Postnatal onset of retinal degeneration by loss of embryonic Ezh2 repression of Six1. Sci Report. doi:10.1038/srep33887; (Cheng L, Wong LJ, Yan N, Han RC et al. Ezh2 does not mediate retinal ganglion cell homeostasis or their susceptibility to injury. PLoS One 2018;13(2):e0191853.). In this study, we used RNA-seq to define up- and down regulated genes in both Ezh2 and G9a deficient (Math5Cre; Ezh2f/fG9af/+; dKO) retinal ganglion cells (RGC) to evaluate the hypothesis of Ezh2 and G9a interaction that has been discussed in other tissues but in the retina. ChIP-Seq was applied to evaluate H3K27me3 histone marks in retinal ganglion cells in wild type (WT), Ezh2 (Math5Cre; Ezh2-/-, sKO) and combined G9a-Ezh2 (Math5Cre; G9a+/-Ezh2-/-, dKO) knockout mutant mice at P1.
2022-07-26 | GSE136360 | GEO
Project description:Cellular binary fate decisions require the progeny to silence genes associated with the alternative fate. The major subsets of alpha:beta T cells have been extensively studied as a model system for fate decisions. While the transcription factor RUNX3 is required for the initiation of Cd4 silencing in CD8 T cell progenitors, it is not required to maintain the silencing of Cd4 and other helper T lineage genes. The other runt domain containing protein, RUNX1, silences Cd4 in an earlier T cell progenitor, but this silencing is reversed whereas the gene silencing after RUNX3 expression is not reverse. Therefore, we hypothesized that RUNX3 and not RUNX1 recruits other factors that maintains the silencing of helper T lineage genes in CD8 T cells. To this end, we performed a proteomics screen of RUNX1 and RUNX3 to determine candidate silencing factors.
2019-11-12 | PXD007511 | Pride
Project description:The epigenetic mechanisms that enable specialized astrocytes to retain neurogenic competence throughout adult life are still poorly understood. Here we show that astrocytes that serve as neural stem cells (NSCs) in the adult mouse subventricular zone (SVZ) express the histone methyltransferase EZH2. This Polycomb repressive factor is required for neurogenesis independent of its role in SVZ NSC proliferation, as Ink4a/Arf-deficiency in Ezh2-deleted SVZ NSCs rescues cell proliferation, but neurogenesis remains defective. Olig2 is a direct target of EZH2, and repression of this bHLH transcription factor is critical for neuronal differentiation. Furthermore, Ezh2 prevents the inappropriate activation of genes that specify non-SVZ neuronal subtypes. In the human brain, SVZ cells including local astroglia also express EZH2, correlating with postnatal neurogenesis. Thus, EZH2 is an epigenetic regulator that distinguishes neurogenic SVZ astrocytes, orchestrating distinct and separable aspects of adult stem cell biology, which has important implications for regenerative medicine and oncogenesis. Examination of histone modifications (H3K27me3 and H3K4me3) in subventricular zone neural stem cells
2014-05-02 | E-GEOD-56394 | biostudies-arrayexpress