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GSE25518
Homo sapiens
23 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Despite timely and successful surgery, 32% of patients with bilateral and 10% with unilateral cryptorchidism will develop azoospermia. Cryptorchid boys at risk of azoospermia display a typical testicular histology of impaired mini-puberty at the time of the orchidopexy.
Publication Title
Testicular gene expression in cryptorchid boys at risk of azoospermia.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 11 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Drosophila heterochromatin protein 1- HP11 is believed to be involved in active transcription, transcriptional gene silencing, and the formation of heterochromatin2-7. However, little is known about the function of HP1 during development. Using a Gal4-induced RNA interference system, we show that conditional depletion of HP1 in transgenic flies results in preferential lethality in male flies. Cytological analysis of mitotic chromosomes reveals that HP1 depletion causes sex-biased chromosomal defects, including telomere fusions. The global levels of specific histone modifications, particularly the hallmarks of active chromatin, are preferentially increased in males as well. Expression analysis revealed that approximately twice as many genes are specifically regulated by HP1 in males compared to females. Furthermore, HP1-regulated genes showed greater enrichment for HP1 binding in males. Taken together, these results reveal that HP1 modulates chromosomal integrity, histone modifications, and transcription in a sex-specific manner.
Publication Title
Sex-specific role of Drosophila melanogaster HP1 in regulating chromatin structure and gene transcription.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
RHAU (RNA helicase-associated with AU-rich element) is a DExH protein that was originally identified as a factor accelerating AU-rich element-mediated mRNA degradation. The finding that RHAU is predominantly localized in the nucleus, despite that mRNA degradation occurs in cytoplasm, prompted us to consider nuclear functions of RHAU. In HeLa cells, RHAU was localized throughout the nucleoplasm with some concentration in nuclear speckles in a manner dependent on ATPase activity. Transcriptional arrest altered its localization to nucleolar caps where it was colocalized with other RNA helicases, p68 and p72, suggesting that RHAU is involved in transcription-related RNA metabolism in the nucleus. To see whether RHAU affects global gene expression either transcriptionally or posttranscriptionally, we performed microarray analysis using total RNA prepared from RHAU-depleted HeLa cell lines, measuring both steady-state mRNA levels and mRNA half-lives by ActinomycinD-chase. We found that most transcripts whose steady-state levels were affected by RHAU knockdown did not show changes in their half-lives, suggesting the involvement of transcriptional regulation for these transcripts. We propose that RHAU has dual functions involved in synthesis and degradation of mRNA in different subcellular compartments.
Publication Title
Transcription-dependent nucleolar cap localization and possible nuclear function of DExH RNA helicase RHAU.
Sample Metadata Fields
Sex
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
The replication of a genomic region during S-phase can be highly dynamic between cell types that differ in transcriptome and epigenome. Replication timing has been positively correlated with several histone modifications that occur at active genes, while repressive histone modifications mark late replicating regions. This raises the question if chromatin modulates the initiating events of replication. To gain insights into this question we have studied the function of heterochromatin protein 1 (HP1), a reader of to the repressive histone lysine 9 methylation of H3, in genome-wide organization of replication. Cells with reduced levels of HP1 show an advanced replication timing of centromeric repeats in agreement with the model that repressive chromatin mediates the very late replication of large clusters of constitutive heterochromatin. Surprisingly however regions with high levels of interspersed repeats on the chromosomal arms in particular on chromosome 4 and in pericentromeric regions of chromosome 2 behave differently. Here loss of HP1 results in delayed replication timing. The fact that these regions are bound by HP1 suggests a direct effect. Thus while HP1 mediates very late replication of centromeric DNA it is also required for early replication of autosomal regions with high levels of repeats. This observation of opposing functions of HP1 suggests a model where repeat inactivation on autosomes is required for proper activation of origins of replication that fire early, while HP1 mediated repression at constitutive heterochromatin is required to ensure replication of centromeric repeats at the end of S phase.
Publication Title
Heterochromatin protein 1 (HP1) modulates replication timing of the Drosophila genome.
Sample Metadata Fields
Sex, Specimen part
View Samples- Oryza sativa
- 12 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Magnaporthe oryzae causes rice blast, the most devastating foliar fungal disease of cultivated rice. During disease development the fungus simultaneously maintains both biotrophic and necrotrophic growth corresponding to a hemi-biotrophic life style. The ability of M. oryzae to also colonize roots and subsequently develop blast symptoms on aerial tissue has been recognized. The fungal root infection strategy and the respective host responses are currently unknown. Global temporal expression analysis suggested a purely biotrophic infection process reflected by the rapid induction of defense response-associated genes at the early stage of root invasion and subsequent repression coinciding with the onset of intracellular fungal growth. The same group of down-regulated defense genes was increasingly induced upon leaf infection by M. oryzae where symptom development occurs shortly post tissue penetration. Our molecular analysis therefore demonstrates the existence of fundamentally different tissue-specific fungal infection strategies and provides the basis for enhancing our understanding of the pathogen life style.
Publication Title
Tissue-adapted invasion strategies of the rice blast fungus Magnaporthe oryzae.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 10 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Duplication of eukaryotic genomes during S phase is coordinated in space and time. In order to identify zones of initiation and cell-type as well as gender-specific plasticity of DNA replication, we profiled replication timing, histone acetylation and transcription throughout the Drosophila genome. We observed two waves of replication initiation with many distinct zones firing in early and multiple, less defined peaks at the end of S phase, suggesting that initiation becomes more promiscuous at the end of S phase. A comparison of different cell types revealed widespread plasticity of replication timing on autosomes. Most occur in large regions but only half coincide with local differences in transcription. In contrast to confined autosomal differences, a global shift in replication timing occurs throughout the single male X chromosome. Unlike in females, the dosage compensated X chromosome replicates almost exclusively early. This difference occurs at sites which are not transcriptionally hyperactivated, but show increased acetylation of lysine 16 of histone H4. This suggests a transcription-independent, yet chromosome-wide process related to chromatin. Importantly, H4K16ac is also enriched at initiation zones as well as early replicating regions on autosomes during S phase. Together, our data reveal novel organizational principles of DNA replication of the Drosophila genome and imply chromatin structure as a determinant of replication timing locally and chromosome-wide.
Publication Title
Chromatin state marks cell-type- and gender-specific replication of the Drosophila genome.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
4T1 mouse mammary carcinoma cells have an autocrine FGFR active loop leading to constitutive activation of downstream signaling pathways. We found that FGFR inhibitors have a strong effect on the proliferation and survival of these cells.
Publication Title
Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
4T1 mouse mammary carcinoma cells have an autocrine FGFR active loop leading to constitutive activation of downstream signaling pathways. We found that FGFR inhibitors have a strong effect on 4T1 tumors in-vivo.
Publication Title
Targeting fibroblast growth factor receptors blocks PI3K/AKT signaling, induces apoptosis, and impairs mammary tumor outgrowth and metastasis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 74 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease worldwide. The current standard therapy for chronic hepatitis C (CHC) consists of a combination of pegylated IFN alpha (pegIFN-alpha) and ribavirin. It achieves a sustained viral clearance in only 5060% of patients. To learn more about molecular mechanisms underlying treatment failure, we investigated IFN-induced signaling in paired liver biopsies collected from CHC patients before and after administration of pegIFN-alpha. In patients with a rapid virological response to treatment, pegIFN-alpha induced a strong up-regulation of IFN-stimulated genes (ISGs). As shown previously, nonresponders had high expression levels of ISGs before therapy. Analysis of posttreatment biopsies of these patients revealed that pegIFN-alpha did not induce expression of ISGs above the pretreatment levels. In accordance with ISG expression data, phosphorylation, DNA binding, and nuclear localization of STAT1 indicated that the IFN signaling pathway in nonresponsive patients is preactivated and refractory to further stimulation. Some features characteristic of nonresponders were more accentuated in patients infected with HCV genotypes 1 and 4 compared with genotypes 2 and 3, providing a possible explanation for the poor response of the former group to therapy. Taken together with previous findings, our data support the concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway.
Publication Title
Interferon signaling and treatment outcome in chronic hepatitis C.
Sample Metadata Fields
No sample metadata fields
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