Genome-nuclear lamina interactions in the heart at embryonic days E9.5 and E12.5
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE64148 | GEO | 2018/12/01
REPOSITORIES: GEO
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Project description:Analysis of whole hearts from e9.5 embryos from Nkx2.5Cre; Hdac3f/f embryos and littermate controls. Results provide insight into gene programs regulated by Hdac3 in cardiac development. Progenitor cells require coordinated expression of lineage-specific genes to regulate differentiation into daughter cell types. Epigenetic regulators are ideally positioned to synchronize transcription of disparate genomic loci. Using cardiac development to model progenitor cell behavior, we demonstrate that Histone deacetylase 3 (Hdac3) functions in a deacetylase-independent manner to repress cardiac differentiation. Loss of Hdac3 promotes differentiation into cardiomyocytes by de-repressing a myocyte gene program.
2018-10-10 | GSE64146 | GEO
Project description:Progenitor cells require coordinated expression of lineage-specific programs, and the nuclear lamina has emerged as an important scaffold for organizing chromatin in many cell types. These ChIP-seq experiments accompany a study focused on defining nuclear organization changes during cardiac development. Specifically, these experiments map the binding sites of LaminB (a key nuclear lamina protein) and H3K9me2 (a histone modification enriched at the nuclear periphery) in mouse ESCs and ESC-derived cardiac myocytes. The observations of these experiments, within the context of the study, indicate that changes in the organization of key genes and cell-type specific genes occurs during cardiogenesis.
2017-10-12 | GSE97877 | GEO
Project description:Mice lacking the zinc finger transcription factor Specificity protein 3 (Sp3) die prenatally in the C57Bl/6 background. To elucidate the cause of mortality we analyzed the potential role of Sp3 in embryonic heart development. Sp3 null hearts display defective looping at E10.5, and at E14.5 the Sp3 null mutants have developed a range of severe cardiac malformations. In an attempt to position Sp3 in the cardiac developmental hierarchy, we analysed the expression patterns of >15 marker genes in Sp3 null hearts. Expression of Cardiac ankyrin repeat protein (Carp) was downregulated prematurely after E12.5, while expression of the other marker genes was not affected. ChIP analysis revealed that Sp3 is bound to the Carp promoter region in vivo. Microarray analysis indicates that small molecule metabolism and cell-cell interactions are the most significantly affected biological processes in E12.5 Sp3 null myocardium. Since the epicardium showed distension from the myocardium, we studied expression of Wt1, a marker for epicardial cells. Wt1 expression was diminished in epicardium-derived cells in the myocardium of Sp3 null hearts. We conclude that Sp3 is required for normal cardiac development, and suggest that it has a crucial role in myocardial differentiation. ( Keywords: Transcription factors, Sp3, knockout mice, cardiac malformations, E12.5
2007-11-01 | GSE9124 | GEO
Project description:Mice lacking the zinc finger transcription factor Specificity protein 3 (Sp3) die prenatally in the C57Bl/6 background. To elucidate the cause of mortality we analyzed the potential role of Sp3 in embryonic heart development. Sp3 null hearts display defective looping at E10.5, and at E14.5 the Sp3 null mutants have developed a range of severe cardiac malformations. In an attempt to position Sp3 in the cardiac developmental hierarchy, we analysed the expression patterns of >15 marker genes in Sp3 null hearts. Expression of Cardiac ankyrin repeat protein (Carp) was downregulated prematurely after E12.5, while expression of the other marker genes was not affected. ChIP analysis revealed that Sp3 is bound to the Carp promoter region in vivo. Microarray analysis indicates that small molecule metabolism and cell-cell interactions are the most significantly affected biological processes in E12.5 Sp3 null myocardium. Since the epicardium showed distension from the myocardium, we studied expression of Wt1, a marker for epicardial cells. Wt1 expression was diminished in epicardium-derived cells in the myocardium of Sp3 null hearts. We conclude that Sp3 is required for normal cardiac development, and suggest that it has a crucial role in myocardial differentiation. ( Experiment Overall Design: Hearts were dissected from E12.5 wildtype (n=3) and Sp3 knockout (n=3) fetuses. Total RNA was isolated from individual hearts; 5μg was used for labelling and hybridization to 430 2.0 Gene Chips (a total of 6).
2008-06-17 | E-GEOD-9124 | biostudies-arrayexpress
Project description:Progenitor cells require coordinated expression of lineage-specific programs, and the nuclear lamina has emerged as an important scaffold for organizing chromatin in many cell types. These transcriptome profiling experiments accompany a study focused on defining nuclear organization changes during cardiac development. This dataset defines gene expression changes induced by Hdac3 deletion during early stages of cardiogenesis, modeled using ESC differentiation assays.
2017-10-12 | GSE97753 | GEO
Project description:E9.5 yolk sacs were collected from wild type (CD1) and Cdx-mutant (DKO) embryos and processed for RNA-sequencing to identify Cdx-dependent changes in gene expression
2022-02-01 | GSE181090 | 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:Genome-nuclear lamina interactions regulate progenitor cell lineage restriction during cardiogenesis
| PRJNA383129 | ENA
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.
2012-03-15 | GSE29992 | GEO
Project description:Hypoxia is an important environmental cue in heart development. Despite of extensive characterization of gain and loss of function models, there is disagreement about the impact of HIF1 signaling elimination during cardiac development. Here, we used new conditional knock out models of Hif1α in Nkx2.5 cardiac progenitors and cardiomyocytes to assess the morphological and functional consequences of HIF1α loss in the developing heart. By combining histology, electron microscopy and high-throughput genomics and proteomics, we found that deletion of Hif1α leads to impaired embryonic glycolysis without influencing cardiomyocyte proliferation and results in an increased mitochondrial number, activation of a transient amino acid response and temporal upregulation of HIF2α and ATF4 by E12.5. Hif1α mutants display normal expression of genes and proteins involved in fatty acid oxidation and do not show any sign of cardiac dysfunction in the adulthood. Our results demonstrate that cardiac HIF1 signaling is dispensable for heart development and reveal the metabolic flexibility of the embryonic myocardium, opening the potential application of alternative energy sources as therapeutic interventions during ischemic events.
2021-01-21 | GSE164453 | GEO