Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparison of exon profiles before and after hormone induction

ABSTRACT: Exon array analysis component. Development, differentiation, and response to environmental stimuli are characterized by sequential changes in cellular state initiated by the de novo binding of induced or temporally regulated transcriptional factors to their cognate genomic sites. The mechanism whereby a given regulatory factor selects a limited number of in vivo targets from myriads of potential genomic binding sites is undetermined. Here we show that up to 95% of induced de novo genomic binding by the glucocorticoid receptor, a paradigmatic ligandactivated transcription factor, is targeted to preexisting foci of accessible chromatin. Factor binding invariably potentiates chromatin accessibility. Cellselective de novo genomic occupancy patterns appear to be comprehensively predetermined by cellspecific differences in baseline chromatin accessibility patterns, with secondary contributions from local sequence features. The results define a novel framework for understanding regulatory factorgenome interactions, and provide a molecular basis for the tissueselectivity of steroid pharmaceuticals and other agents that intersect the living genome. Time course of dexamethasone treatment of 2 cell types from a zero hour untreated control, 2 hour, 4 hour and 8hr treatment times. This is part of a larger study: Chromatin accessibility predetermines de novo steroid receptor binding. There are 2 replicates per cell line per time point except in the case of 8hr Dex treated AtT-20 where a second replicate was unavailable.

ORGANISM(S): Mus musculus

SUBMITTER: Richard Sandstrom

PROVIDER: E-GEOD-26189 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Comparison of gene expression profiles for hormone induction in the presence and absence of AP1 binding.

Project description:Gene expression array analysis component. Ligand-dependent transcription by the nuclear receptor glucocorticoid receptor (GR) is mediated by interactions with co-regulators. The role of these interactions in determining selective binding of GR to regulatory elements remains unclear. Recent findings indicate a large fraction of genomic GR binding coincides with chromatin that is accessible prior to hormone treatment, suggesting that receptor binding is dictated by proteins that maintain chromatin in an open state. Combining nucleolytic cleavage and chromatin immunoprecipitation with high-throughput sequencing, we identify the activator protein 1 (AP1) as a major partner for productive GR-chromatin interactions. AP1 is critical for GR-regulated transcription and recruitment to co-occupied regulatory elements, illustrating an extensive AP1-GR interaction network. Importantly, the maintenance of baseline chromatin accessibility facilitates GR recruitment and is dependent on AP1 binding. We propose a model where the basal occupancy of transcription factors act to prime chromatin and direct inducible transcription factors to select regions in the genome. Dexamethasone treatment of cells at zero hour untreated control and 4 hour treatment times, in the absence and presence of acidic-fos (A-fos), an AP1 dominant negative. A-fos expression is under tetracycline control (Tet-Off). This is part of a larger study: Transcription Factor AP1 Potentiates Chromatin Accessibility and Glucocorticoid Receptor Binding. There are 2 replicates per condition per time point.

2011-06-30 | E-GEOD-29983 | biostudies-arrayexpress

Comparison of exon profiles before and after hormone induction

Project description:Exon array analysis component. Development, differentiation, and response to environmental stimuli are characterized by sequential changes in cellular state initiated by the de novo binding of induced or temporally regulated transcriptional factors to their cognate genomic sites. The mechanism whereby a given regulatory factor selects a limited number of in vivo targets from myriads of potential genomic binding sites is undetermined. Here we show that up to 95% of induced de novo genomic binding by the glucocorticoid receptor, a paradigmatic ligandactivated transcription factor, is targeted to preexisting foci of accessible chromatin. Factor binding invariably potentiates chromatin accessibility. Cellselective de novo genomic occupancy patterns appear to be comprehensively predetermined by cellspecific differences in baseline chromatin accessibility patterns, with secondary contributions from local sequence features. The results define a novel framework for understanding regulatory factorgenome interactions, and provide a molecular basis for the tissueselectivity of steroid pharmaceuticals and other agents that intersect the living genome.

2010-12-21 | GSE26189 | GEO

Evolution of diapause in the African killifish by remodeling ancient gene regulatory landscape

Project description:Suspended animation (e.g. hibernation, diapause) allows organisms to survive extreme environments. But the mechanisms underlying the evolution of suspended animation states are unknown. The African turquoise killifish has evolved diapause as a form of suspended development to survive the complete drought that occurs every summer. Here, we show that gene duplicates – paralogs – exhibit specialized expression in diapause compared to normal development in the African turquoise killifish. Surprisingly, paralogs with specialized expression in diapause are evolutionarily very ancient and are present even in vertebrates that do not exhibit diapause. To determine if evolution of diapause is due to the regulatory landscape rewiring at ancient paralogs, we assessed chromatin accessibility genome-wide in fish species with or without diapause. This analysis revealed an evolutionary recent increase in chromatin accessibility at very ancient paralogs in African turquoise killifish. The increase in chromatin accessibility is linked to the presence of new binding sites for transcription factors, likely due to de novo mutations and transposable element (TE) insertion. Interestingly, accessible chromatin regions in diapause are enriched for lipid metabolism genes, and our lipidomics studies uncover a striking difference in lipid species in African turquoise killifish diapause, which could be critical for long-term survival. Together, our results show that diapause likely originated by repurposing pre-existing gene programs via recent changes in the regulatory landscape. This work raises the possibility that suspended animation programs could be reactivated in other species for long-term preservation via transcription factor remodeling and suggests a mechanism for how complex adaptations evolve in nature.

2021-08-05 | ST001898 | MetabolomicsWorkbench

De novo mutations in the genome organizer CTCF cause Intellectual Disability (RNA-Seq)

Project description:An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift mutations and one de novo missense mutation in the CTCF gene in individuals with intellectual disability, microcephaly and growth retardation. Furthermore, a patient with a larger deletion including CTCF was identified. CTCF (CCCTC-binding factor) is one of the most important chromatin organizers in vertebrates and is involved in various chromatin regulation processes such as higher order of chromatin organization, enhancer function, and maintenance of three-dimensional chromatin structure. Transcriptome analyses in all three patients with point mutations revealed deregulation of genes involved in signal transduction and emphasized the role of CTCF in enhancer-driven expression of genes. Our findings indicate that haploinsufficiency of CTCF affects genomic interaction of enhancers and their regulated gene promoters that drive developmental processes and cognition. Comparison of lymphocyte gene expression between 3 de novo CTCF mutation patients and 8 controls (4 technical replicates each, no biological replicates).

2013-06-01 | E-GEOD-46831 | biostudies-arrayexpress

De novo mutations in the genome organizer CTCF cause Intellectual Disability (ChIP-Seq)

Project description:An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift mutations and one de novo missense mutation in the CTCF gene in individuals with intellectual disability, microcephaly and growth retardation. Furthermore, a patient with a larger deletion including CTCF was identified. CTCF (CCCTC-binding factor) is one of the most important chromatin organizers in vertebrates and is involved in various chromatin regulation processes such as higher order of chromatin organization, enhancer function, and maintenance of three-dimensional chromatin structure. Transcriptome analyses in all three patients with point mutations revealed deregulation of genes involved in signal transduction and emphasized the role of CTCF in enhancer-driven expression of genes. Our findings indicate that haploinsufficiency of CTCF affects genomic interaction of enhancers and their regulated gene promoters that drive developmental processes and cognition. ChIP-seq analysis of CTCF genomic binding sites in lymphocytes of a control individual (no replicates).

2013-06-01 | E-GEOD-46832 | biostudies-arrayexpress

SUMOylation regulates chromatin protein network and accessibility at glucocorticoid receptor-binding sites

Project description:Glucocorticoid receptor (GR) is an essential transcription factor (TF), controlling metabolism, development and immune responses. SUMOylation regulates chromatin occupancy and target gene expression of GR in a locus-selective manner, but the mechanism of regulation has remained elusive. Here, we show using selective isolation of chromatin-associated proteins that the protein network around chromatin-bound GR is affected by SUMOylation, with several nuclear receptor coregulators and chromatin modifiers being more avidly associated with SUMOylation-deficient than SUMOylation competent GR. This difference is reflected in our chromatin accessibility and gene expression data, showing that the SUMOylation-deficient GR is more potent in opening chromatin at glucocorticoid-regulated enhancers and inducing expression of their target loci. Our results thus show that SUMOylation determines GR specificity by regulating the chromatin protein network and accessibility at GR-driven enhancers. We speculate that a similar mechanism is utilized by many other SUMOylated TFs.

2021-09-08 | PXD015183 | Pride

SPOCD1 is a novel executor of piRNA-directed DNA methylation that links MIWI2 to the de novo DNA methylation machiner

Project description:In mammals, the acquisition of the germline from the soma provides the germline with an essential challenge, the necessity to erase and reset genomic methylation. In the male germline RNA-directed DNA methylation silences young active transposable elements (TEs). The PIWI protein MIWI2 (PIWIL4) and its associated PIWI-interacting RNAs (piRNAs) are proposed to tether MIWI2 to nascent TE transcripts and instruct DNA methylation. The mechanism by which MIWI2 directs de novo TE methylation is poorly understood but central to the immortality of the germline. Here, we define the interactome of MIWI2 in foetal gonocytes that are undergoing de novo genome methylation and identify a novel MIWI2-associated factor, SPOCD1, that is essential for young TE methylation and silencing. The loss of Spocd1 in mice results in male specific infertility and does not impact on piRNA biogenesis nor localization of MIWI2 to the nucleus. SPOCD1 is a nuclear protein and its expression is restricted to the period of de novo genome methylation. We found SPOCD1 co-purified in vivo with DNMT3L and DNMT3A, components of the de novo methylation machinery as well as constituents of the NURD and BAF chromatin remodelling complexes. We propose a model whereby tethering of MIWI2 to a nascent TE transcript recruits repressive chromatin remodelling activities and the de novo methylation apparatus through its association with SPOCD1. In summary, we have identified a novel and essential executor of mammalian piRNA-directed DNA methylation.

2020-06-22 | PXD016701 | Pride

Developmental dynamics of DNA accessibility during flower development [DNaseI-Seq]

Project description:Development of eukaryotic organisms is controlled by transcription factors that trigger specific and global changes in gene expression programmes. In plants, MADS-domain transcription factors act as master regulators of developmental switches and organ specification. However, the mechanisms by which these factors dynamically regulate the expression of their target genes at different developmental stages are still poorly understood. Here, we characterize the dynamic relationship of chromatin accessibility, gene expression and DNA-binding of two MADS-domain proteins during Arabidopsis flower development. The developmental dynamics of DNA-binding of APETALA1 and SEPALLATA3 is largely independent of chromatin accessibility, and our findings suggest that AP1 acts as M-bM-^@M-^Xpioneer factorM-bM-^@M-^Y that modulates chromatin accessibility, thereby facilitating access of other transcriptional regulators to their target genes. Our data provide a primer to the idea that cellular differentiation in plants can be associated to dynamic changes in chromatin accessibility, as consequence of the action of master transcription factors. We used the AP1-GR system to conduct DNaseI hypersensitivity experiments at different stages of flower development. Samples were generated from tissue in which the AP1-GR protein was induced using a treatment of 1 uM DEX to the shoot apex. The material was collect before treatment and 2, 4 and 8 days after treatment. As control, naked DNA from wild-type inflorescences was used. Experiments were done in two biological replicates. The GSE47981 includes expression data that are complementary to the data in the GSE46986 and GSE46894.

2014-02-03 | E-GEOD-46894 | biostudies-arrayexpress

Developmental dynamics of floral gene regulation [ChIP-Seq]

Project description:Development of eukaryotic organisms is controlled by transcription factors that trigger specific and global changes in gene expression programmes. In plants, MADS-domain transcription factors act as master regulators of developmental switches and organ specification. However, the mechanisms by which these factors dynamically regulate the expression of their target genes at different developmental stages are still poorly understood. Here, we characterize the dynamic relationship of chromatin accessibility, gene expression and DNA-binding of two MADS-domain proteins during Arabidopsis flower development. The developmental dynamics of DNA-binding of APETALA1 and SEPALLATA3 is largely independent of chromatin accessibility, and our findings suggest that AP1 acts as 'pioneer factor' that modulates chromatin accessibility, thereby facilitating access of other transcriptional regulators to their target genes. Our data provide a primer to the idea that cellular differentiation in plants can be associated to dynamic changes in chromatin accessibility, as consequence of the action of master transcription factors. We used the AP1-GR system to conduct chromatin immunoprecipitation experiments with SEP3-specific antibodies and GR atibodies followed by deep-sequencing (ChIP-Seq) in order to determine SEP3 and AP1 binding sites on a genome-wide scale. Samples were generated from tissue in which the AP1-GR protein was induced using a treatment of 1 uM DEX to the shoot apex. The material was collect 2, 4 and 8 days after treatment. As control, we performed ChIP experiments using pre-immune serum at the different time points. Experiments were done in two biological replicates for 4 days and 8 days time-points while one biological replicate was done for control samples and 2 days time-point. The GSE47981 includes expression data that are complementary to the data in the GSE46986 and GSE46894.

2014-02-03 | E-GEOD-46986 | biostudies-arrayexpress

DNase02

Project description:In eukaryotes, DNA is packaged into chromatin. It has become evident that the degree of packaging is not uniform along the genome. More compact chromatin greatly hinder access of transcription factors or other DNA-binding or modifying proteins, and DNA accessibility is an important yet poorly studied layer of regulation. The aim of the study was to map DNA accessibility in chromatin of Arabidopsis leaf nuclei using DNaseI sensitivity as a proxy for accessibility. Chromatin was digested with DnaseI and genomic fragments of >17kb were hybridized to AGRONOMICS1 tiling arrays.

2013-05-01 | E-TABM-1219 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data