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PROVIDER: PRJNA127711 | ENA |
REPOSITORIES: ENA
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Project description:Background: In addition to determining static states of gene expression (high vs. low), it is important to characterize their dynamic status. For example, genes with H3K27me3 chromatin marks are not only suppressed but also poised for activation. However, the responsiveness of genes to perturbations has never been studied systematically. To distinguish gene responses to specific factors from responsiveness in general, it is necessary to analyze gene expression profiles of cells responding to a large variety of disturbances, and such databases did not exist before. Results: We estimated the responsiveness of all genes in mouse ES cells using our recently published database on expression change after controlled induction of 53 transcription factors (TFs) and other genes. Responsive genes (/N/ = 4746), which were readily upregulated or downregulated depending on the kind of perturbation, mostly have regulatory functions and a propensity to become tissue-specific upon differentiation. Tissue-specific expression was evaluated on the basis of published (GNF) and our new data for 15 organs and tissues. Non-responsive genes (/N/ = 9562), which did not change their expression much following any perturbation, were enriched in housekeeping functions. We found that TF-responsiveness in ES cells is the best predictor known for tissue-specificity in gene expression. Among genes with CpG islands, high responsiveness is strongly associated with H3K27me3 chromatin marks, and low responsiveness is associated with H3K36me3 chromatin, binding of E2F1, and GABP binding motifs in promoters. Conclusions: We thus propose the responsiveness of expression to perturbations as a new way to define the dynamic status of genes, which brings new insights into mechanisms of regulation of gene expression and tissue specificity. This SuperSeries is composed of the following subset Series: GSE19806: Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity (1 of 2) GSE19814: Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity (2 of 2) Refer to individual Series
2011-02-14 | E-GEOD-22151 | biostudies-arrayexpress
Project description:Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity (2 of 2)
| PRJNA129755 | ENA
Project description:Responsiveness of genes to manipulation of transcription factors in ES cells is associated with histone modifications and tissue specificity (1 of 2)
| PRJNA129745 | ENA
Project description:BACKGROUND: In addition to determining static states of gene expression (high vs. low), it is important to characterize their dynamic status. For example, genes with H3K27me3 chromatin marks are not only suppressed but also poised for activation. However, the responsiveness of genes to perturbations has never been studied systematically. To distinguish gene responses to specific factors from responsiveness in general, it is necessary to analyze gene expression profiles of cells responding to a large variety of disturbances, and such databases did not exist before. RESULTS: We estimated the responsiveness of all genes in mouse ES cells using our recently published database on expression change after controlled induction of 53 transcription factors (TFs) and other genes. Responsive genes (N = 4746), which were readily upregulated or downregulated depending on the kind of perturbation, mostly have regulatory functions and a propensity to become tissue-specific upon differentiation. Tissue-specific expression was evaluated on the basis of published (GNF) and our new data for 15 organs and tissues. Non-responsive genes (N = 9562), which did not change their expression much following any perturbation, were enriched in housekeeping functions. We found that TF-responsiveness in ES cells is the best predictor known for tissue-specificity in gene expression. Among genes with CpG islands, high responsiveness is associated with H3K27me3 chromatin marks, and low responsiveness is associated with H3K36me3 chromatin, stronger tri-methylation of H3K4, binding of E2F1, and GABP binding motifs in promoters. CONCLUSIONS: We thus propose the responsiveness of expression to perturbations as a new way to define the dynamic status of genes, which brings new insights into mechanisms of regulation of gene expression and tissue specificity. Total RNA was isolated by TRIzol (Invitrogen) after 2 days. Cy3-CTP labeled sample targets were prepared with total RNA by Low RNA Input Fluorescent Linear Amplification Kit (Agilent). Cy5-CTP labeled reference target was produced from mixture of Stratagene Universal Mouse Reference RNA and MC1 cells RNA. Most samples were collected in 2 replications taken from different animals, except bone and fat, which had only one replication.
2011-02-11 | E-GEOD-19806 | biostudies-arrayexpress
Project description:Background: In addition to determining static states of gene expression (high vs. low), it is important to characterize their dynamic status. For example, genes with H3K27me3 chromatin marks are not only suppressed but also poised for activation. However, the responsiveness of genes to perturbations has never been studied systematically. To distinguish gene responses to specific factors from responsiveness in general, it is necessary to analyze gene expression profiles of cells responding to a large variety of disturbances, and such databases did not exist before. Results: We estimated the responsiveness of all genes in mouse ES cells using our recently published database on expression change after controlled induction of 53 transcription factors (TFs) and other genes. Responsive genes (/N/ = 4746), which were readily upregulated or downregulated depending on the kind of perturbation, mostly have regulatory functions and a propensity to become tissue-specific upon differentiation. Tissue-specific expression was evaluated on the basis of published (GNF) and our new data for 15 organs and tissues. Non-responsive genes (/N/ = 9562), which did not change their expression much following any perturbation, were enriched in housekeeping functions. We found that TF-responsiveness in ES cells is the best predictor known for tissue-specificity in gene expression. Among genes with CpG islands, high responsiveness is strongly associated with H3K27me3 chromatin marks, and low responsiveness is associated with H3K36me3 chromatin, binding of E2F1, and GABP binding motifs in promoters. Conclusions: We thus propose the responsiveness of expression to perturbations as a new way to define the dynamic status of genes, which brings new insights into mechanisms of regulation of gene expression and tissue specificity. This SuperSeries is composed of the SubSeries listed below.
2011-02-14 | GSE22151 | GEO
Project description:BACKGROUND: In addition to determining static states of gene expression (high vs. low), it is important to characterize their dynamic status. For example, genes with H3K27me3 chromatin marks are not only suppressed but also poised for activation. However, the responsiveness of genes to perturbations has never been studied systematically. To distinguish gene responses to specific factors from responsiveness in general, it is necessary to analyze gene expression profiles of cells responding to a large variety of disturbances, and such databases did not exist before. RESULTS: We estimated the responsiveness of all genes in mouse ES cells using our recently published database on expression change after controlled induction of 53 transcription factors (TFs) and other genes. Responsive genes (N = 4746), which were readily upregulated or downregulated depending on the kind of perturbation, mostly have regulatory functions and a propensity to become tissue-specific upon differentiation. Tissue-specific expression was evaluated on the basis of published (GNF) and our new data for 15 organs and tissues. Non-responsive genes (N = 9562), which did not change their expression much following any perturbation, were enriched in housekeeping functions. We found that TF-responsiveness in ES cells is the best predictor known for tissue-specificity in gene expression. Among genes with CpG islands, high responsiveness is associated with H3K27me3 chromatin marks, and low responsiveness is associated with H3K36me3 chromatin, stronger tri-methylation of H3K4, binding of E2F1, and GABP binding motifs in promoters. CONCLUSIONS: We thus propose the responsiveness of expression to perturbations as a new way to define the dynamic status of genes, which brings new insights into mechanisms of regulation of gene expression and tissue specificity.
2011-02-11 | GSE19806 | GEO
Project description:BACKGROUND: In addition to determining static states of gene expression (high vs. low), it is important to characterize their dynamic status. For example, genes with H3K27me3 chromatin marks are not only suppressed but also poised for activation. However, the responsiveness of genes to perturbations has never been studied systematically. To distinguish gene responses to specific factors from responsiveness in general, it is necessary to analyze gene expression profiles of cells responding to a large variety of disturbances, and such databases did not exist before. RESULTS: We estimated the responsiveness of all genes in mouse ES cells using our recently published database on expression change after controlled induction of 53 transcription factors (TFs) and other genes. Responsive genes (N = 4746), which were readily upregulated or downregulated depending on the kind of perturbation, mostly have regulatory functions and a propensity to become tissue-specific upon differentiation. Tissue-specific expression was evaluated on the basis of published (GNF) and our new data for 15 organs and tissues. Non-responsive genes (N = 9562), which did not change their expression much following any perturbation, were enriched in housekeeping functions. We found that TF-responsiveness in ES cells is the best predictor known for tissue-specificity in gene expression. Among genes with CpG islands, high responsiveness is associated with H3K27me3 chromatin marks, and low responsiveness is associated with H3K36me3 chromatin, stronger tri-methylation of H3K4, binding of E2F1, and GABP binding motifs in promoters. CONCLUSIONS: We thus propose the responsiveness of expression to perturbations as a new way to define the dynamic status of genes, which brings new insights into mechanisms of regulation of gene expression and tissue specificity Inhibitors of cell signaling are known to support the pluripotent state of embryonic stem cells (Ying et al. 2008, Nature 453, 519-523, PMID: 18497825). To characterize the effect of inhibitors on the gene expression we treated B6R(5) mouse ES cells (C57BL/6 strain) with FGFR inhibitor PD173074 (100 uM), MEK inhibitor PD98059 (25 uM),and GSK-3 inhibitor BIO (2 uM) 24 hr after plating. Cells were grown without feeders on gelatin coated, 6-well plates, 100,000 cells/well (10^4 cells/cm2), in complete ES medium at 37 0C; 5% CO2. Medium was changed daily. Inhibitors dissolved in DMSO were added 24 hr after plating and cells were harvested 48 hr after treatment (72 hr after plating). Control cells were treated with DMSO. Keywords: cell type comparison design,reference design Total RNA was isolated by TRIzol (Invitrogen) after 2 days. Cy3-CTP labeled sample targets were prepared with total RNA by Low RNA Input Fluorescent Linear Amplification Kit (Agilent). Cy5-CTP labeled reference target was Stratagene Universal Mouse Reference RNA.
2011-02-11 | E-GEOD-19814 | biostudies-arrayexpress
Project description:BACKGROUND: In addition to determining static states of gene expression (high vs. low), it is important to characterize their dynamic status. For example, genes with H3K27me3 chromatin marks are not only suppressed but also poised for activation. However, the responsiveness of genes to perturbations has never been studied systematically. To distinguish gene responses to specific factors from responsiveness in general, it is necessary to analyze gene expression profiles of cells responding to a large variety of disturbances, and such databases did not exist before. RESULTS: We estimated the responsiveness of all genes in mouse ES cells using our recently published database on expression change after controlled induction of 53 transcription factors (TFs) and other genes. Responsive genes (N = 4746), which were readily upregulated or downregulated depending on the kind of perturbation, mostly have regulatory functions and a propensity to become tissue-specific upon differentiation. Tissue-specific expression was evaluated on the basis of published (GNF) and our new data for 15 organs and tissues. Non-responsive genes (N = 9562), which did not change their expression much following any perturbation, were enriched in housekeeping functions. We found that TF-responsiveness in ES cells is the best predictor known for tissue-specificity in gene expression. Among genes with CpG islands, high responsiveness is associated with H3K27me3 chromatin marks, and low responsiveness is associated with H3K36me3 chromatin, stronger tri-methylation of H3K4, binding of E2F1, and GABP binding motifs in promoters. CONCLUSIONS: We thus propose the responsiveness of expression to perturbations as a new way to define the dynamic status of genes, which brings new insights into mechanisms of regulation of gene expression and tissue specificity Inhibitors of cell signaling are known to support the pluripotent state of embryonic stem cells (Ying et al. 2008, Nature 453, 519-523, PMID: 18497825). To characterize the effect of inhibitors on the gene expression we treated B6R(5) mouse ES cells (C57BL/6 strain) with FGFR inhibitor PD173074 (100 uM), MEK inhibitor PD98059 (25 uM),and GSK-3 inhibitor BIO (2 uM) 24 hr after plating. Cells were grown without feeders on gelatin coated, 6-well plates, 100,000 cells/well (10^4 cells/cm2), in complete ES medium at 37 0C; 5% CO2. Medium was changed daily. Inhibitors dissolved in DMSO were added 24 hr after plating and cells were harvested 48 hr after treatment (72 hr after plating). Control cells were treated with DMSO. Keywords: cell type comparison design,reference design
2011-02-11 | GSE19814 | GEO
Project description:Stem and progenitor cells undergo a global elevation of nascent transcription, or hypertranscription, during key developmental transitions involving rapid cell proliferation. The chromatin remodeler Chd1 binds to RNA Pol I and II genes and is required for hypertranscription in embryonic stem (ES) cells in vitro and the early post-implantation epiblast in vivo. Biochemically, Chd1 has been shown to facilitate transcription at least in part by removing nucleosomal barriers to elongation, but its mechanism of action in stem cells remains poorly understood. Here we report a novel role for Chd1 in the repair of promoter-proximal endogenous double-stranded DNA breaks (DSBs) in ES cells. An unbiased proteomics approach revealed that Chd1 interacts with several DNA repair factors including ATM, Parp1, Kap1 and Topoisomerase 2. We show that wild-type ES cells display high levels of phosphorylated H2AX and Kap1 at chromatin, notably at rDNA in the nucleolus, in a Chd1-dependent manner. Loss of Chd1 leads to an extensive accumulation of DSBs at Chd1 target Pol II genes and rDNA. Genes prone to DNA breaks in Chd1-null ES cells tend to be longer genes with GC-rich promoters, a more labile nucleosomal structure and roles in chromatin organization, transcription and signaling. These results reveal a vulnerability of hypertranscribing stem cells to endogenous DNA breaks, with important implications for developmental and cancer biology.
2021-06-14 | PXD024604 | Pride
Project description:The structure of chromatin is critical for many aspects of cellular physiology and is considered to be the primary medium to store epigenetic information. It is defined by the histone molecules that constitute the nucleosome, the positioning of the nucleosomes along the DNA and the non-histone proteins that associate with it. These factors help to establish and maintain a largely DNA sequence-independent but surprisingly stable structure. Chromatin is extensively disassembled and reassembled during DNA replication, repair, recombination or transcription in order to allow the necessary factors to gain access to their substrate. Despite such constant interference with chromatin structure, the epigenetic information is generally well maintained. Surprisingly, the mechanisms that coordinate chromatin assembly and ensure proper assembly are not particularly well understood. Here, we use SWATH-MS to describe the kinetics of in vitro assembled chromatin supported by an embryo extract prepared from preblastoderm Drosophila melanogaster embryos. This system allows easy manipulation of distinct aspects of chromatin assembly such as post-translational histone modifications, the levels of histone chaperones and the concentration of distinct DNA binding factors. Our findings support the idea that chromatin assembly factors and factors important for chromatin structure bind chromatin in an ordered manner, which is -at least in part- regulated by histone deacetylation. We are able to identify functional clusters of proteins based on their different binding kinetics. Whereas many proteins bind exclusively during the onset of chromatin assembly, a few proteins show a clear tendency towards matured chromatin.
2016-01-27 | PXD002537 | Pride