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SRP047365
Mus musculus
18 Downloadable Samples
Illumina HiSeq 2000
Description
Ionizing radiation (IR) has long been associated with reduced hematopoietic function and increased malignancies, although the mechanisms behind this relationship remain poorly understood. The carcinogenic effect of IR has been commonly attributed to the direct induction of DNA damage. We demonstrate that IR exposure results in long-term, somatically heritable, cell-intrinsic reductions in HSC self-renewal that is mediated by C/EBPa and reversed by Notch, both of which are associated with human leukemias. Remarkably, restoration of HSC self-renewal prevents selection for C/EBPa loss of function in previously irradiated HSC pools. We propose that environmental insults prompt HSC to initiate a program limiting their self-renewal to prevent damaged HSC from contributing to hematopoiesis. This "programmed mediocrity" is advantageous for the localized insults animals have evolved to deal with, but becomes tumor promoting when the entire HSC compartment is damaged, such as during total body irradiation, by increasing selective pressure for adaptive oncogenic mutations Overall design: Examination of mRNA levels in in vitro and in vivo Hematopoietic Stem Cell that exposed to IR Ionizing radiation (IR) or control. Each group has three replicates.
Publication Title
Contrasting roles for C/EBPα and Notch in irradiation-induced multipotent hematopoietic progenitor cell defects.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 31 Downloadable Samples
Arabidopsis Gene 1.1 ST Array (aragene11st)
Description
Brassinosteroids (BRs) are growth-promoting plant hormones that play a role in abiotic stress responses, but molecular modes that enable this activity remain largely unknown. Here we show that BRs participate in the regulation of freezing tolerance. BR signaling-defective mutants of Arabidopsis thaliana were hypersensitive to freezing before and after cold acclimation. The constitutive activation of BR signaling, in contrast, enhanced freezing resistance. Evidence is provided that the BR-controlled basic helixloophelix transcription factor CESTA (CES) can contribute to the constitutive expression of the C-REPEAT/DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR (CBF) transcriptional regulators that control cold responsive (COR) gene expression. In addition, CBF-independent classes of BR-regulated COR genes are identified that are regulated in a BR- and CES-dependent manner during cold acclimation. A model is presented in which BRs govern different cold-responsive transcriptional cascades through the posttranslational modification of CES and redundantly acting factors. This contributes to the basal resistance against freezing stress, but also to the further improvement of this resistance through cold acclimation.
Publication Title
Brassinosteroids participate in the control of basal and acquired freezing tolerance of plants.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 21 Downloadable Samples
Arabidopsis Gene 1.1 ST Array (aragene11st), Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Small Molecule Hyperphyllin Enhances Leaf Formation Rate and Mimics Shoot Meristem Integrity Defects Associated with AMP1 Deficiency.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Arabidopsis Gene 1.1 ST Array (aragene11st)
Description
ALTERED MERISTEM PROGRAM1 (AMP1) is a member of the M28 family of carboxypeptidases with a pivotal role in plant development and stress adaptation. Its most prominent mutant defect is a unique hypertrophic shoot phenotype combining a strongly increased organ formation rate with enhanced meristem size and the formation of ectopic meristem poles. However, so far the role of AMP1 in shoot development could not be assigned to a specific molecular pathway nor is its biochemical function resolved. We used a chemical genetic approach to identify the drug hyperphyllin (HP), which specifically mimics the shoot defects of amp1, including plastochron reduction and enlargement and multiplication of the shoot meristem. To further assess whether hyperphyllin acts in an AMP1-dependent manner we compared the transcriptonal responses of hyperphyllin-treated wild-type and amp1 mutant seedlings.
Publication Title
The Small Molecule Hyperphyllin Enhances Leaf Formation Rate and Mimics Shoot Meristem Integrity Defects Associated with AMP1 Deficiency.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 9 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
ALTERED MERISTEM PROGRAM1 (AMP1) is a member of the M28 family of carboxypeptidases with a pivotal role in plant development and stress adaptation. Its most prominent mutant defect is a unique hypertrophic shoot phenotype combining a strongly increased organ formation rate with enhanced meristem size and the formation of ectopic meristem poles. However, so far the role of AMP1 in shoot development could not be assigned to a specific molecular pathway nor is its biochemical function resolved. We used a chemical genetic approach to identify the drug hyperphyllin (HP), which specifically mimics the shoot defects of amp1, including plastochron reduction and enlargement and multiplication of the shoot meristem. To further assess whether hyperphyllin acts in an AMP1-dependent manner we compared the transcriptonal responses of hyperphyllin-treated wild-type Arabidopsis seedlings with those of untreated amp1 mutant seedlings.
Publication Title
The Small Molecule Hyperphyllin Enhances Leaf Formation Rate and Mimics Shoot Meristem Integrity Defects Associated with AMP1 Deficiency.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 9 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
A case of transcriptional gene silencing, originally observed in tetraploid Arabidopsis plants, created an epiallele resistant to many mutations or inhibitor treatments that activate other suppressed genes. This raised the question about the molecular basis of this extreme stability.
Publication Title
Cooperation of multiple chromatin modifications can generate unanticipated stability of epigenetic States in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Although small RNAs efficiently control transposition activity of most transposons in the host genome, such immune system is not always applicable against new transposon's invasions. Here we explored a possibility to introduce potentially mobile copy of the Penelope retroelement previously implicated in hybrid dysgenesis syndrome in Drosophila virilis into the genomes of two distant Drosophila species. The consequences of such introduction were monitored at different phases after experimental colonization as well as in D. virilis species which is apparently in the process of ongoing Penelope invasion. We investigated the expression of Penelope and biogenesis of Penelope-derived small RNAs in D. virilis and D. melanogaster strains originally lacking active copies of this element after experimental Penelope invasion. These strains were transformed by constructs containing intact Penelope copies. We show that immediately after transformation, which imitates the first stage of retroelement invasion, Penelope undergoes transposition predominantly in somatic tissues, and may produce siRNAs that are apparently unable to completely silence its activity. However, at the later stages of colonization Penelope copies may jump into one of the piRNA-clusters, which results in production of homologous piRNAs that are maternally deposited and can silence euchromatic transcriptionally active copies of Penelope in trans and, hence, prevent further amplification of the invader in the host genome. Intact Penelope copies and different classes of Penelope-derived small RNAs were found in most geographical strains of D. virilis collected throughout the world. Importantly, all strains of this species containing full-length Penelope tested do not produce gonadal sterility in dysgenic crosses and, hence, exhibit neutral cytotype. In order to understand whether RNA interference mechanism able to target Penelope operates in related species of the virilis group we correlated the presence of full-length and potentially active Penelope with the occurrence of piRNAs homologous to this TE in the ovaries of species comprising the group. It was demonstrated, that Penelope-derived piRNAs are present in all virilis group species containing full-length but transcriptionally silent copies of this element that probably represent the remnants of its previous invasions taking place in the course of the virilis species divergent evolution. Overall design: piRNA size profile (23-29nt) was examined in D. melanogaster strains, where Penelope-piRNAs are detected by Northern blot
Publication Title
Evolution and dynamics of small RNA response to a retroelement invasion in Drosophila.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Small non-coding RNAs that associate with Piwi proteins, called piRNAs, serve as guides for repression of diverse transposable elements in germ cells of Metazoa. In Drosophila, the genomic regions that give rise to piRNAs, the so-called piRNA clusters, are transcribed to generate long precursor molecules that are processed into mature piRNAs. How genomic regions that give rise to piRNA precursor transcripts are differentiated from the rest of the genome and how these transcripts are specifically channeled into the piRNA biogenesis pathway are not known. We found that trans-generationally inherited piRNAs provide the critical trigger for piRNA production from homologous genomic regions in the next generation by two different mechanisms. First, inherited piRNAs enhance processing of homologous transcripts into mature piRNAs by initiating the ping-pong cycle in the cytoplasm. Second, inherited piRNAs induce installment of the H3K9me3 mark on genomic piRNA cluster sequences. The HP1 homolog Rhino binds to the H3K9me3 mark through its chromodomain and is enriched over piRNA clusters. Rhino recruits the piRNA biogenesis factor Cutoff to piRNA clusters and is required for efficient transcription of piRNA precursors. We propose that trans-generationally inherited piRNAs act as an epigenetic memory for identification of substrates for piRNA biogenesis on two levels, by inducing a permissive chromatin environment for piRNA precursor synthesis and by enhancing processing of these precursors. Overall design: total RNA sequencing of RNA from ovaries of cuff+/- or cuff-/- flies
Publication Title
Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Small non-coding RNAs that associate with Piwi proteins, called piRNAs, serve as guides for repression of diverse transposable elements in germ cells of Metazoa. In Drosophila, the genomic regions that give rise to piRNAs, the so-called piRNA clusters, are transcribed to generate long precursor molecules that are processed into mature piRNAs. How genomic regions that give rise to piRNA precursor transcripts are differentiated from the rest of the genome and how these transcripts are specifically channeled into the piRNA biogenesis pathway are not known. We found that trans-generationally inherited piRNAs provide the critical trigger for piRNA production from homologous genomic regions in the next generation by two different mechanisms. First, inherited piRNAs enhance processing of homologous transcripts into mature piRNAs by initiating the ping-pong cycle in the cytoplasm. Second, inherited piRNAs induce installment of the H3K9me3 mark on genomic piRNA cluster sequences. The HP1 homolog Rhino binds to the H3K9me3 mark through its chromodomain and is enriched over piRNA clusters. Rhino recruits the piRNA biogenesis factor Cutoff to piRNA clusters and is required for efficient transcription of piRNA precursors. We propose that trans-generationally inherited piRNAs act as an epigenetic memory for identification of substrates for piRNA biogenesis on two levels, by inducing a permissive chromatin environment for piRNA precursor synthesis and by enhancing processing of these precursors. Overall design: nuclear run-on in wildtype and Rhino knockdown to investigate the transcriptional activity in Rhino knockdown compared to wildtype
Publication Title
Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Small non-coding RNAs that associate with Piwi proteins, called piRNAs, serve as guides for repression of diverse transposable elements in germ cells of Metazoa. In Drosophila, the genomic regions that give rise to piRNAs, the so-called piRNA clusters, are transcribed to generate long precursor molecules that are processed into mature piRNAs. How genomic regions that give rise to piRNA precursor transcripts are differentiated from the rest of the genome and how these transcripts are specifically channeled into the piRNA biogenesis pathway are not known. We found that trans-generationally inherited piRNAs provide the critical trigger for piRNA production from homologous genomic regions in the next generation by two different mechanisms. First, inherited piRNAs enhance processing of homologous transcripts into mature piRNAs by initiating the ping-pong cycle in the cytoplasm. Second, inherited piRNAs induce installment of the H3K9me3 mark on genomic piRNA cluster sequences. The HP1 homolog Rhino binds to the H3K9me3 mark through its chromodomain and is enriched over piRNA clusters. Rhino recruits the piRNA biogenesis factor Cutoff to piRNA clusters and is required for efficient transcription of piRNA precursors. We propose that trans-generationally inherited piRNAs act as an epigenetic memory for identification of substrates for piRNA biogenesis on two levels, by inducing a permissive chromatin environment for piRNA precursor synthesis and by enhancing processing of these precursors. Overall design: total RNA sequencing of RNA from ovaries of shWhite and Rhino knockdown flies
Publication Title
Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing.
Sample Metadata Fields
Specimen part, Subject
View Samples