Spinocerebellar ataxia type 3 (SCA3) is a dominantly inherited neurodegenerative disorder caused by a polyglutamine-encoding CAG repeat expansion in the ATXN3 gene, which encodes a deubiquitinating enzyme, ATXN3, implicated in numerous quality control pathways. Several mechanisms have been proposed to explain the pathogenic role of mutant polyQ-expanded ATXN3 in SCA3 including disease protein aggregation, impairment of ubiquitin-proteasomal degradation and transcriptional dysregulation. A better understanding of the normal functions of this protein may shed light on SCA3 disease pathogenesis. To assess the potential normal role of ATXN3 in regulating transcription, we compared gene expression profiles in wildtype (WT) versus Atxn3 knockout (KO) mouse embryonic fibroblasts (MEFs).
Loss of the Spinocerebellar Ataxia type 3 disease protein ATXN3 alters transcription of multiple signal transduction pathways.
Specimen part
View SamplesCD138+ B220- plasma cells were sorted from bone marrow and B220+ CD23+ mature follicular B cells were sorted from the spleens. Plasma cells were sorted from C57BL/6 mice 7 days after boosting with antigen, with mice first primed with an i.p. injection of KLH/IFA followed by boost at day 21 with KLH/PBS i.p. Mature B cells were sorted from antigen-nave C57BL/6 mice.
Heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) and elongation factor, RNA polymerase II, 2 (ELL2) are regulators of mRNA processing in plasma cells.
Specimen part
View SamplesSmall 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
Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing.
Specimen part, Subject
View SamplesSmall 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
Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing.
Specimen part, Subject
View SamplesSmall 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
Transgenerationally inherited piRNAs trigger piRNA biogenesis by changing the chromatin of piRNA clusters and inducing precursor processing.
Specimen part, Subject
View SamplesThe Microrchidia (Morc) family of GHKL ATPases are present in a wide variety of prokaryotic and eukaryotic organisms but are of largely unknown function. Genetic screens in Arabidopsis thaliana have identified Morc genes as important repressors of transposons and other DNA methylated and silent genes. MORC1 deficient mice were previously found to display male-specific germ cell loss and infertility. Here we show that MORC1 is responsible for transposon repression in the male germline in a pattern that is similar to that observed for germ cells deficient for the DNA methyltransferase homolog DNMT3L. Morc1 mutants show highly localized defects in the establishment of DNA methylation at specific classes of transposons, and this is associated with failed transposon silencing at these sites. Our results identify MORC1 as an important new regulator of the epigenetic landscape of male germ cells during the period of global de novo methylation. Overall design: This data includes: 47 RNA-seq, 4 smRNA-seq, 6 BS-seq, and 2 ChIP-seq datasets
MORC1 represses transposable elements in the mouse male germline.
No sample metadata fields
View SamplesBovine leukemia virus (BLV) Tax is a transcriptional activator of viral replication and a key contributor to oncogenic potential. We previously identified interesting mutant forms of Tax with elevated (TaxD247G) or reduced (TaxS240P) transactivation effects on BLV replication and propagation. In this study, to identify genes that play a role in the cascade of signal events regulated by wild-type and mutant Tax proteins, we used a large-scale host cell gene-profiling approach.
Identification of bovine leukemia virus tax function associated with host cell transcription, signaling, stress response and immune response pathway by microarray-based gene expression analysis.
Cell line
View SamplesHuman T cell leukemia virus type 1 (HTLV-1) Tax is potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. In this study, a large-scale host cell signaling events related to cellular proliferation were used to identify genes involved in Tax-mediated cell signaling events related to cellular proliferation and apoptosis.
Visualizing spatiotemporal dynamics of apoptosis after G1 arrest by human T cell leukemia virus type 1 Tax and insights into gene expression changes using microarray-based gene expression analysis.
Cell line
View SamplesMuscle biopsies from biceps and deltoid were taken from 5 patients with FSHD, 5 asymptomatic carriers and 5 normal controls. The genome-wide expression patterns were compared using Affymetrix U133 Plus 2.0 chips.
Transcriptional regulation differs in affected facioscapulohumeral muscular dystrophy patients compared to asymptomatic related carriers.
Sex, Age, Specimen part, Disease
View SamplesBisphenol A (BPA), an endocrine-disrupting chemical (EDC), is a well-known, ubiquitous estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we first examined the alterations of in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS).
Endocrine disrupter bisphenol A increases in situ estrogen production in the mouse urogenital sinus.
Specimen part
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