This SuperSeries is composed of the SubSeries listed below.
Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes.
Specimen part
View SamplesDNA methylation and the Polycomb Repression System are epigenetic mechanisms that play important roles in maintaining transcriptional repression. Recent evidence suggests that DNA methylation can attenuate the binding of Polycomb protein components to chromatin and thus plays a role in determining their genomic targeting. However, whether this role of DNA methylation is important in the context of transcriptional regulation is unclear. By genome-wide mapping of the Polycomb Repressive Complex 2 (PRC2)-signature histone mark, H3K27me3, in severely DNA hypomethylated mouse somatic cells, we show that hypomethylation leads to widespread H3K27me3 redistribution, in a manner that reflects the local DNA methylation status in wild-type cells. Unexpectedly, we observe striking loss of H3K27me3 and PRC2 from Polycomb-target gene promoters in DNA hypomethylated cells, including Hox gene clusters. Importantly, we show that many of these genes become ectopically expressed in DNA hypomethylated cells, consistent with loss of Polycomb-mediated repression. An intact DNA methylome is required for appropriate Polycomb-mediated gene repression by constraining PRC2 targeting. These observations identify a previously unappreciated role for DNA methylation in gene regulation and therefore influence our understanding of how this epigenetic mechanism contributes to normal development and disease.
Redistribution of H3K27me3 upon DNA hypomethylation results in de-repression of Polycomb target genes.
Specimen part
View SamplesSle1c is a sublocus of the NZM2410-derived Sle1 major susceptibility locus. We have previously shown that Sle1c contributes to lupus pathogenesis by conferring CD4+ T cell-intrinsic hyperactivation and increased susceptibility to chronic graft-versus-host disease (cGVHD) that mapped to the centromeric portion of the locus. In this study, we have refined the centromeric sublocus to a 675Kb interval, termed Sle1c2. Recombinant congenic strains expressing Sle1c2 exhibited a T cell-intrinsic CD4+ T cell hyperactivation and cGVHD susceptibility, similar to mice with the parental Sle1c.
Murine lupus susceptibility locus Sle1c2 mediates CD4+ T cell activation and maps to estrogen-related receptor γ.
Sex, Age, Specimen part
View SamplesThe goal of our study was to evaluate at the systems-level, the effect of sex hormones on thymic epithelial cells (TECs). To this end, we sequenced the transcriptome of cortical and medullary TECs (cTECs and mTECs) from three groups of 6 month-old mice: males, females and males castrated at four weeks of age. In parallel, we analyzed variations in the size of TEC subsets in those three groups between 1 and 12 months of age. We report that sex hormones have pervasive effects on the transcriptome of TECs: the number of differentially expressed genes was 1,440 in cTECs and 1,783 in mTECs. Sexual dimorphism was particularly conspicuous in cTECs. Male cTECs displayed low proliferation rates that correlated with low expression of Foxn1 and its main targets. Furthermore, male cTECs expressed relatively low levels of genes instrumental in thymocyte expansion (e.g., Dll4) and positive selection (Psmb11 and Ctsl). Nevertheless, cTECs were more abundant in males than females. Accumulation of cTECs in males correlated with differential expression of genes regulating cell survival and cell differentiation. Unexpectedly, we observed that female and male sex hormones repressed promiscuous gene expression in mTECs. Since sex hormones did not affect the expression of Aire per se, they must impinge on the activity of unidentified regulator(s) of promiscuous gene expression in mTECs. The sexual dimorphism of TECs highlighted here may be mechanistically linked to the well-recognized sex differences in susceptibility to infections and autoimmune diseases. Overall design: Cortical and medullary thymic epithelial cells from 6 month-old male, female and castrated male mice were sequenced in 3 replicates (but only 2 replicates for castrated male mTECs).
Thymic Mesenchymal Cells Have a Distinct Transcriptomic Profile.
No sample metadata fields
View SamplesA soybean ortholog of the Arabidopsis MADS-domain transcription factor (called GmAGL15) enhanced somatic embryogenesis from immature cotyledon explants of soybean when expressed via the 35S promoter compared to non transgenic tissue (cultivar Jack). To better understand how this occurs an expression microarray experiment was performed.
Alterations in the transcriptome of soybean in response to enhanced somatic embryogenesis promoted by orthologs of Agamous-like15 and Agamous-like18.
Specimen part, Time
View SamplesThymocytes were extracted from a pool of three 8-12 week old C57BL-6 female mice. Cells were separated from stroma by gently crushing the thymi in between 2 microslides. RNA from thymocytes was extracted using the Trizol reagent and protocol, and analysed using the Illumina HiSeq 2000. Overall design: Transcriptomic analysis of a single replicate of thymocytes from a pool of three 8-12 week old C57BL-6 female mice, using the Illumina HiSeq 2000
Thymic Mesenchymal Cells Have a Distinct Transcriptomic Profile.
Specimen part, Cell line, Subject
View SamplesA mutant previously isolated from a screen of EMS-mutagenized Arabidopsis lines, per1, showed normal root hair development under control conditions but displayed an inhibited root hair elongation phenotype upon Pi deficiency. Additionally, the per1 mutant exhibited a pleiotropic phenotype under control conditions, resembling Pi-deficient plants in several aspects. Under Pi deficiency, the accumulation of Pi and iron was increased in the mutant when compared to the wild-type. Inhibition of root hair elongation upon growth on low Pi media was reverted by treatment with the Pi analog phosphite, suggesting that the mutant phenotype is not the result of a defect in Pi sensing. Reciprocal grafting experiments revealed that the mutant rootstock is sufficient to cause the phenotype. Transcriptional profiling of per1 and wild-type plants subjected to short-term Pi starvation revealed genes that may be important for the signaling of Pi deficiency. We conclude that UBP14 function is crucial for adapting root development to the prevailing local availability of phosphate.
Ubiquitin-specific protease 14 (UBP14) is involved in root responses to phosphate deficiency in Arabidopsis.
Specimen part
View SamplesMuscle satellite cells are a self-renewing pool of stem cells that give rise to daughter myogenic precursor cells in adult skeletal muscle. Published and preliminary data indicated that MyoD and p53 genes are involved in satellite cell differentiation. We would like to know what downstream genes of both transcription factors are affected in satellite cell-derived myoblasts (MyoD-/-, p53 -/-).
MyoD induces myogenic differentiation through cooperation of its NH2- and COOH-terminal regions.
No sample metadata fields
View SamplesThe Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS, DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D).
Sequential treatment with cytarabine and decitabine has an increased anti-leukemia effect compared to cytarabine alone in xenograft models of childhood acute myeloid leukemia.
Specimen part, Disease
View SamplesSkeletal muscle senescence influences whole organism aging, yet little is known on the relay of pro-longevity signals from muscles to other tissues. We performed an RNAi screen in Drosophila for muscle-released cytokines (?myokines?) regulating lifespan and identified Myoglianin, the homolog of human Myostatin. Myoglianin is induced in skeletal muscles by the transcription factor Mnt and together they constitute an inter-organ signaling module that regulates lifespan, age-related muscle dysfunction, and protein synthesis across aging tissues. Both Mnt and Myoglianin activate already in young age the protective decline in protein synthesis that is typical of old age, while knock-down of Myoglianin impairs this process. Mechanistically, Mnt decreases the expression of nucleolar components in muscles while also decreasing nucleolar size in distant tissues via Myostatin/p38 MAPK signaling. Our results highlight a myokine-dependent inter-organ longevity pathway that coordinates nucleolar function and protein synthesis across aging tissues.
Intertissue control of the nucleolus via a myokine-dependent longevity pathway.
Sex, Specimen part, Treatment
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