microRNAs (miRNAs) are small non-coding RNAs that function in literally all cellular processes. miRNAs interact with Argonaute (Ago) proteins and guide them to specific target sites located in the 3’ untranslated region (UTR) of target mRNAs leading to translational repression and deadenylation-induced mRNA degradation. Most miRNAs are processed from hairpin-structured precursors by the consecutive action of the RNase III enzymes Drosha and Dicer. However, processing of miR-451 is Dicer-independent and cleavage is mediated by the endonuclease Ago2. Here we have characterized miR-451 sequence and structure requirements for processing as well as sorting of miRNAs into different Ago proteins. Pre-miR-451 appears to be optimized for Ago2 cleavage and changes result in reduced processing. In addition, we show that the mature miR-451 only associates with Ago2 suggesting that mature miRNAs are not exchanged between different members of the Ago protein family. Based on cloning and deep sequencing of endogenous miRNAs associated with Ago1-3, we do not find evidence for miRNA sorting in human cells. However, Ago identity appears to influence the length of some miRNAs, while others remain unaffected. Overall design: Examination of miRNAs associated with endogenous human Ago1-4 in HeLa cells
microRNAs associated with the different human Argonaute proteins.
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View SamplesTo identify epigenetically silenced genes in multiple myeloma (MM) cell lines and to determine the effects of 5-aza-2-deoxycytidine and trichostatin A on gene expression. We treated 3 multiple myeloma cell lines (MM1, NCI-H929, U266) with 5-aza-2-deoxycytidine and/or trichostatin A.
Genome-wide transcriptional response to 5-aza-2'-deoxycytidine and trichostatin a in multiple myeloma cells.
Specimen part, Disease, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory.
Specimen part
View SamplesDuring acute viral infections, nave CD8+ T cells differentiate into effector CD8+ T cells and, after viral control, into memory CD8+ T cells. Memory CD8+ T cells are highly functional, proliferate rapidly upon reinfection and persist long-term without antigen. In contrast, during chronic infections, CD8+ T cells become exhausted and have poor effector function, express multiple inhibitory receptors, possess low proliferative capacity, and cannot persist without antigen. To compare the development of functional memory T cells with poorly functional exhausted T cells, we generated longitudinal transcriptional profiles for each.
Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory.
Specimen part
View SamplesThe essential thiol antioxidant, glutathione (GSH) is recruited into the nucleus of mammalian cells early in cell proliferation, suggesting a key role of the nuclear thiol pool in cell cycle regulation. However, the functions of nuclear GSH (GSHn) and its integration with the cytoplasmic GSH (GSHc) pools in whole cell redox homeostasis and signaling are unknown. Here we show that GSH is recruited into the nucleus early in cell proliferation in Arabidopsis thaliana, confirming the requirement for localization of GSH in the nucleus as a universal feature of cell cycle regulation.
Recruitment of glutathione into the nucleus during cell proliferation adjusts whole-cell redox homeostasis in Arabidopsis thaliana and lowers the oxidative defence shield.
Treatment
View SamplesWe have used repetitive elements, including retrotransposons, as model loci to address how and when heterochromatin forms during development. High throughput RNA-sequencing using a Nano-CAGE protocol throughout early embryogenesis revealed that the expression of repetitive elements is abundant in embryonic cells, highly dynamic and stage-specific, with most repetitive elements becoming repressed before implantation. Furthermore, we show that Line L1 elements and IAP retrotransposons become reactivated from both parental genomes in mouse embryos after fertilisation, indicating an open chromatin configuration at the beginning of development. Our data show that the reprogramming process that follows fertilisation is accompanied by a robust transcriptional activation of retrotransposons and suggests that expression of repetitive elements is initially regulated through an RNA-dependent mechanism in mammals. Overall design: Genome Wide profiling of CAGE transcripts using Nano-CAGE and RNAseq in oocytes and 3 different stages of mouse pre-implantation development
Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA.
Age, Specimen part, Cell line, Subject
View SamplesIn this study gene expression of monocyte-derived macrophages (MDM) from chronic obstructive pulmonary disease (COPD) patients and healthy subjects was investigated. MDM were treated with LPS, a combination of fine TiO2 and ultrafine Printex90 particles, or remained untreated.
Tissue-specific induction of ADAMTS2 in monocytes and macrophages by glucocorticoids.
No sample metadata fields
View SamplesComparison between cell lines from 9 different cancer tissue of origin types (Breast, Central Nervous System, Colon, Leukemia, Melanoma, Non-Small Cell Lung, Ovarian, Prostate, Renal) from NCI-60 panel
Multifactorial regulation of E-cadherin expression: an integrative study.
Sex, Age, Specimen part, Disease, Disease stage, Cell line, Time
View SamplesWe report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations. Overall design: GMP and MEP were isolated from Runx1+/+-Tg(vav-Cre) and Runx1fl/fl-Tg(vav-Cre) mice as well as Runx1fl/fl-Tg(vav-Cre) XMP, total RNA extracted and sequenced
Runx1 downregulates stem cell and megakaryocytic transcription programs that support niche interactions.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Sex, Age, Specimen part, Treatment
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