We 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 SamplesmicroRNAs (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.
No sample metadata fields
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 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 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
View SamplesHdac1 and 2 are important regulators of developmental processes. In this study we created microglia specific compound Hdac1 and Hdac2 knock out mice. Pre-natal ablation of both Hdac1 and 2 from microglia leads to reduced cell number and altered cell morphology. To investigate how Hdac1 and 2 knock out in microglia alters cellular gene expression profile we carried out RNA-seq analysis at different time points. Overall design: We used FACS sorted microglia cells from control and Hdac1/2fl/flCx3cr1Cre (constituitive knockout) or Hdac1/2fl/flCx3cr1CreERT2 (inducible) mice at different time points viz. Embryonic day 16 (E16 - inducible knockout only), Post natal day 0 (P0), 2 and 6 weeks after birth
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Age, Treatment, Subject
View SamplesEpigenetic alterations has been implicated in the pathology of several neurodegenerative diseases. To investigate the role of microglial Hdac1 and 2 in the pathogenesis of Alzheimer's disease (AD), we created microglia specific compound Hdac1 and Hdac2 knock out mice in 5X FAD background. Genetic ablation of Hdac1 and 2 from microglia reduced amyloid plaque burden and improved spatial learning and memory function.
Histone Deacetylases 1 and 2 Regulate Microglia Function during Development, Homeostasis, and Neurodegeneration in a Context-Dependent Manner.
Sex, Specimen part
View Samples