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PROVIDER: PRJNA137471 | ENA |
REPOSITORIES: ENA
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Project description:The spatial and temporal control of gene expression during development requires the concerted actions of sequence-specific transcriptional regulators and epigenetic chromatin modifiers, which are thought to function within precise nuclear compartments. However, how these activities are coordinated within the dynamic context of the nuclear environment is still largely unresolved. Here we show that transcriptional repression by the Msx1 homeoprotein coordinates recruitment of Polycomb to genomic targets with localization to the nuclear periphery. Using genome-wide ChIP-Seq analyses to identify genomic binding sites for Msx1, we find that repressed target genes are enriched at the nuclear periphery in myoblast cells. We further show that the interaction of Msx1 with the Polycomb repressive complex PRC2 is required for transcriptional repression and regulation of myoblast differentiation, and promotes increased tri-methylation of lysine 27 on histone H3 (H3K27me3) at Msx1 target genes. Furthermore, Msx1 genomic binding promotes the dynamic spatial redistribution of the H3K27me3 repressive mark to the nuclear periphery in developing embryos in vivo. Thus, our findings suggest a hitherto unappreciated spatial coordination of transcription factor binding, Polycomb recruitment, and subnuclear localization in regulation of developmentgene expression programs. In order to identify genes regulated by Msx1, we infected C2C12 myoblast cells with a retrovirus expressing a tamoxifen-regulated Msx1 protein, Msx1-ER (or with empty vector as a control), followed by induction with 0.2 nM of tamoxifen or vehicle (DMSO) for 6 hours. Regulated genes were identified as those that changed in expression upon tamoxifen induction of the Msx1-ER protein but did not change in the empty vector control. Experiments were performed in triplicate for each of the four experimental conditions (Msx1-ER + tamoxifen, Msx1-ER - tamoxifen, empty vector control + tamoxifen, empty vector control - tamoxifen), for a total of 12 independent array samples. This submission represents the transcriptome component of the study.
2011-08-16 | E-GEOD-26021 | biostudies-arrayexpress
Project description:The spatial and temporal control of gene expression during development requires the concerted actions of sequence-specific transcriptional regulators and epigenetic chromatin modifiers, which are thought to function within precise nuclear compartments. However, how these activities are coordinated within the dynamic context of the nuclear environment is still largely unresolved. Here we show that transcriptional repression by the Msx1 homeoprotein coordinates recruitment of Polycomb to genomic targets with localization to the nuclear periphery. We used genome-wide ChIP-Seq analyses to identify genomic binding sites for Msx1 in C2C12 murine myoblast cells.
2011-08-17 | GSE26711 | GEO
Project description:The spatial and temporal control of gene expression during development requires the concerted actions of sequence-specific transcriptional regulators and epigenetic chromatin modifiers, which are thought to function within precise nuclear compartments. However, how these activities are coordinated within the dynamic context of the nuclear environment is still largely unresolved. Here we show that transcriptional repression by the Msx1 homeoprotein coordinates recruitment of Polycomb to genomic targets with localization to the nuclear periphery. Using genome-wide ChIP-Seq analyses to identify genomic binding sites for Msx1, we find that repressed target genes are enriched at the nuclear periphery in myoblast cells. We further show that the interaction of Msx1 with the Polycomb repressive complex PRC2 is required for transcriptional repression and regulation of myoblast differentiation, and promotes increased tri-methylation of lysine 27 on histone H3 (H3K27me3) at Msx1 target genes. Furthermore, Msx1 genomic binding promotes the dynamic spatial redistribution of the H3K27me3 repressive mark to the nuclear periphery in developing embryos in vivo. Thus, our findings suggest a hitherto unappreciated spatial coordination of transcription factor binding, Polycomb recruitment, and subnuclear localization in regulation of developmentgene expression programs. In order to identify genes regulated by Msx1, we infected C2C12 myoblast cells with a retrovirus expressing a tamoxifen-regulated Msx1 protein, Msx1-ER (or with empty vector as a control), followed by induction with 0.2 nM of tamoxifen or vehicle (DMSO) for 6 hours. Regulated genes were identified as those that changed in expression upon tamoxifen induction of the Msx1-ER protein but did not change in the empty vector control.
2011-08-17 | GSE26021 | GEO
Project description:The spatial and temporal control of gene expression during development requires the concerted actions of sequence-specific transcriptional regulators and epigenetic chromatin modifiers, which are thought to function within precise nuclear compartments. However, how these activities are coordinated within the dynamic context of the nuclear environment is still largely unresolved. Here we show that transcriptional repression by the Msx1 homeoprotein coordinates recruitment of Polycomb to genomic targets with localization to the nuclear periphery. We used genome-wide ChIP-Seq analyses to identify genomic binding sites for Msx1 in C2C12 murine myoblast cells. C2C12 myoblast cells were seeded at a density of 2.5 x 10^5 cells / 10-cm plate one day prior to infection, and infected with a retrovirus containing a Flag-Msx1 construct for two consecutive days. The resulting cells were then crosslinked with formaldehyde, and DNA was enriched by chromatin immunoprecipitation (ChIP) with an anti-Flag antibody and analyzed by Solexa sequencing. Enriched regions were identified using a Poissonian background model, and were further compared to an additional background of sequences from a sample of Flag-immunoprecipitated DNA from C2C12 cells infected with an empty vector to determine enrichment. ChIP was performed using an antibody against the Flag epitope (Sigma M2, F3165).
2011-08-17 | E-GEOD-26711 | biostudies-arrayexpress
Project description:The homeoprotein Msx1 and Msx2 involved in normal skeletal muscle development and also contribute to muscle defects if altered during development. Deciphering the downstream signaling networks of Msx1 and Msx2 in myoblasts differentiation will help us to understand the molecular events that contribute to muscle defects. The objective of this study was to evaluate the proteomics characteristics in Msx1 and Msx2 mediated myoblasts differentiation, using isobaric tags for the relative and absolute quantification labelling technique (iTRAQ). The results showed that 1535 proteins with quantitative information were obtained. Volcano plots illustrated, in undifferentiated stage, 32 common downstream regulatory proteins for Msx1 and Msx2, 39 specific regulatory proteins for Msx1, and 13 specific for Msx2. While, in differentiated stage, 17 common downstream regulatory proteins for Msx1 and Msx2, 10 specific regulatory proteins for Msx1, and 21 specific for Msx2. Gene ontology, KEGG pathway and protein-protein interaction networks analyses revealed these proteins primarily associated with Arginine and proline metabolism, Glycolysis/Gluconeogenesis, Fatty acid degradation, Metabolism of xenobiotics by cytochrome P450 and Apoptosis. In addition, our data shows Acta1 was probably a core of the downstream regulatory networks of Msx1 and Msx2 in skeletal muscle development. The findings will help us to understand the molecular roles of Msx1 and Msx2 during muscle development as well as regeneration, and to understand the molecular events that contribute to muscle defects.
2023-07-20 | PXD026944 | Pride
Project description:Polycomb-lamina antagonism partitions heterochromatin at the nuclear periphery
| PRJNA747066 | ENA
Project description:Transcriptionally silent chromatin often localizes at the nuclear periphery, but whether post-transcriptional gene repression also occurs at the nuclear envelope (NE) remains unknown. Here we demonstrate that the NE protein Lem2 cooperates with the nuclear exosome in RNA degradation. Loss of Lem2 causes the accumulation of non-coding RNAs and meiotic transcripts. We demonstrate that an engineered exosome RNA substrate preferentially localizes at the nuclear periphery dependent on Lem2. While Lem2 itself does not bind RNA, it physically interacts with the exosome-targeting MTREC complex and promotes the recruitment of RNAs. This Lem2-dependent pathway acts separately from nuclear bodies into which exosome factors assemble, revealing the existence of multiple degradation pathways. We propose that Lem2 recruits exosome co-factors to the nuclear periphery to coordinate RNA surveillance and fine-tunes the transcriptional program during the switch from mitotic to meiotic growth.
2021-05-31 | GSE174347 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE10697: Self-Self Hybridisation were used to set confidence 99% intervals GSE10698: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 1 GSE10699: The effects of artificial tethering of chromosomes to the nuclear periphery using LacI/lap2b anchorage constructs 2 Background: The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In mammals, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. Methodology: To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells. here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. Principal findings: We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Significance: Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation. Keywords: SuperSeries Refer to individual Series
2010-05-26 | E-GEOD-10701 | biostudies-arrayexpress
Project description:The mandible of the jawed vertebrate is derived from the mandibular process of the first pharyngeal arch of the early embryo. The first pharyngeal arch consists of cells from all three germ layers, with the neural crest giving rise to all the skeletal elements of the mandible. The correct patterning of the neural crest cells by spatially and temporally controlled expression of various transcription factors during mandible development is crucial for the proper morphogenesis of the lower jaw. Msx family genes encode transcription factors which contain the conserved homeodomain. Among the three members of Msx genes, Msx1 and Msx2 are expressed in the neural crest and epithelium of distal mandibular process during early embryonic development with partially overlapped expression patterns. Msx1-/- mouse embryos develop multiple craniofacial developmental defects including tooth agenesis, cleft palate, and hypoplastic mandible. Although no jaw defects were observed in Msx2-/- mouse embryos, Msx1-/-Msx2-/- mouse embryos exhibit significantly severer mandibular defects compared to Msx1-/- mouse embryos, suggesting a partial functional redundancy between the two genes in mandible development. Besides the direct roles of Msx1 and Msx2 in the development of the mandibular neural crest, the phenotypes of Msx1-/-Msx2-/- may also contributed by secondary impacts from defective pre-migrative neural crest and non-neural crest tissues. Here we performed the gene expression profiling by RNA-seq in the distal mandibular processes of Msx1f/f;Msx2f/f;Hand2-Cre and Msx1f/+;Msx2f/f;Hand2-Cre embryos at E10.75, the former developed distally truncated mandible at later stages while the latter served as morphologically normal littermate control. Comparing the gene expression profiles of the two will give us insight into the functions of Msx1 and Msx2 expressed in mandibular neural crest cells in the development of the mandible.
2024-01-10 | GSE222566 | GEO
Project description:Background: The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In mammals, chromosomal regions with low gene-density are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. However, a crucial issue is whether this level of nuclear organisation directly affects gene function, rather than merely reflecting it. Methodology: To directly investigate whether proximity to the nuclear periphery can influence gene expression in mammalian cells. here we relocate specific human chromosomes to the nuclear periphery by tethering them to a protein of the inner nuclear membrane. Principal findings: We show that this can reversibly suppress the expression of some endogenous human genes located near the tethering sites, and even genes further away. However, the expression of many other genes is not detectably reduced and we show that location at the nuclear periphery is not incompatible with active transcription. The dampening of gene expression around the nuclear periphery is dependent on the activity of histone deacetylases. Significance: Our data show that the radial position within the nucleus can influence the expression of some, but not all, genes. This is compatible with the suggestion that re-localisation of genes to the peripheral zone of the nucleus could be used by metazoans to modulate the expression of selected genes during development and differentiation. This SuperSeries is composed of the SubSeries listed below.
2008-03-04 | GSE10701 | GEO