We report the mRNA profile of aged mice (24 months old) fed either a control diet or a diet containing Rapamycin (14 ppm) for 3 months. After drug treatement, the hearts of the mice were removed and total mRNA was removed from the tissue. Analysis revealed that there were 700 significantly differentially expressed genes between the control fed group and the Rapamycin diet group by our analysis. Overall design: Heart tissue samples from age-matched control mice (n=10) and rapamycin fed mice (n=10) were extracted for total RNA. The samples were sequenced using Illumina HiSeq 2000 (50 basepair paired-end sequencing). The sequencing yielded quality scores greater than 30 with an average of 10 million reads per sample. 34,293 genes were mapped back to the MGSCv37 C57BL/6J mouse genome (maximum paired distance=300 and minimum=130, minimum number of reads per mapping = 5, maximum number of mismatches= 2, with the reads being mapped to unique sites in the genome).
Late-life rapamycin treatment reverses age-related heart dysfunction.
Age, Specimen part, Treatment, Subject
View SamplesThe goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL. Overall design: miRNA and mRNA were quantified from whole blood and monocytes of women undergoing spontaneous preterm labor compared to nonlabor controls matched on gestational age
Comparative analysis of gene expression in maternal peripheral blood and monocytes during spontaneous preterm labor.
Subject
View SamplesThe H4K16 acetyltransferase MOF plays a crucial role in dosage compensation in Drosophila, but has additional, global functions in gene control. We compared the molecular context and effect of MOF activity in male and female flies combining chromosome-wide mapping and transcriptome studies with analyses of defined reporter loci in transgenic flies. MOF distributes dynamically between two types of complexes, the Dosage Compensation Complex (DCC) and complexes containing MBD-R2, a global facilitator of transcription. These different targeting principles define the distribution of MOF between the X chromosome and autosomes and at transcription units with 5 or 3 enrichment.
The activation potential of MOF is constrained for dosage compensation.
Cell line
View SamplesOn triggering of the T cell receptor CD8 T lymphocytes downregulate expression of the transcription factor KLF2. KLF2 expression remains low as these cells differentiate to Cytotoxic T lymphocytes (CTL) but may be re-expressed depending on the local environmental signals.
The impact of KLF2 modulation on the transcriptional program and function of CD8 T cells.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The MOF-containing NSL complex associates globally with housekeeping genes, but activates only a defined subset.
Sex, Specimen part, Cell line
View SamplesWe assessed the gene expression profile of purified CD205+CD8+ Dendritic Cells isolated from murine spleens.
NOD2 modulates immune tolerance via the GM-CSF-dependent generation of CD103<sup>+</sup> dendritic cells.
Sex, Age, Specimen part
View SamplesAnalysis of strain-specific differences in gene expression in brains from a hydrocephalic mouse model of primary ciliary dyskinesia. The results identify genes that are differentially expressed between C57BL6/J and 129S6/SvEvTac brains. These genes encode proteins that function in a variety of cellular processes and include some that are relevant to hydrocephalus and cilia function, providing insight into the mechanisms underlying susceptibility to hydrocephalus.
Strain-specific differences in brain gene expression in a hydrocephalic mouse model with motile cilia dysfunction.
Age, Specimen part
View SamplesThe MOF-containing NSL complex binds to many but not all promoters of active genes and potentially contributes to their proper gene expression. It is currently unknown what determines whether an active gene is bound or not. Here, we provide evidence that the NSL complex primarily targets active promoters of most housekeeping genes. There, it co-localizes with the chromatin remodeler NURF and the histone methyltransferase Trithorax. Moreover, despite binding to most housekeeping genes, the NSL complex regulates only a subset of them, which are depleted for certain insulator binding-proteins and enriched for the core promoter motif Ohler 5. We suggest that the combination of general chromatin factors and core promoter motifs is predictive for whether a housekeeping gene is transcriptionally regulated by the NSL complex.
The MOF-containing NSL complex associates globally with housekeeping genes, but activates only a defined subset.
Cell line
View SamplesCombining an in vitro hNCC differentiation protocol with epigenomic profiling, we provide the first whole-genome characterization of cis-regulatory elements in this highly relevant cell type. With this data at hand, we have characterized the chromatin state and dynamics of all human gene promoters during the course of NCC in vitro differentiation. Most importantly, we have identified a large cohort of active and NCC-specific enhancers, which we showed to be functionally relevant in vivo, in the context of embryonic development. Finally, through sequence analysis of the identified NCC enhancers, we uncovered the orphan nuclear receptors NR2F1 and NR2F2 as novel hNCC transcriptional regulators both in vitro and in vivo. Overall design: RNA-seq experiments in human neural crest cells (hNCC)
Epigenomic annotation of enhancers predicts transcriptional regulators of human neural crest.
No sample metadata fields
View SamplesPredicting the impact of cis-regulatory sequence on gene expression is a foundational challenge for biology. We combine polysome profiling of hundreds of thousands of randomized 5' UTRs with deep learning to build a predictive model that relates human 5' UTR sequence to translation. Together with a genetic algorithm, we use the model to engineer new 5? UTRs that accurately target specified levels of ribosome loading, providing the ability to tune sequences for optimal protein expression. We show that the same approach can be extended to chemically modified RNA, an important feature for applications in mRNA therapeutics and synthetic biology. We test 35,000 truncated human 5' UTRs and 3,577 naturally-occurring variants and show that the model accurately predicts ribosome loading of these sequences. Finally, we provide evidence of 47 SNVs associated with human diseases that cause a significant change in ribosome loading and thus a plausible molecular basis for disease. Overall design: Polysom profiling and sequencing was performed using a library of 300,000 randomized 5' UTR 50-mers with eGFP used as the CDS. Three RNA chemistries were tested: unmodified, pseudouridine, and 1-methylpseudouridine. These were performed in duplicate (6 samples total). A designed library that includes human 5' UTRs, SNVs, and sequences engineered with a genetic algorithm was used with the eGFP CDS (no duplicate). A second randomized library used mCherry as the CDS, also performed in duplicate.
Human 5' UTR design and variant effect prediction from a massively parallel translation assay.
Specimen part, Subject
View Samples