The therapeutic potential of pro-resolution factors in determining the outcome of inflammatory events has gained ground over the past decade. However, the attention has been focused on the non-genomic effects of these endogenous, anti-inflammatory substances. In this study, we have focused our attention on identifying specific annexin 1 (AnxA1) protein/ALX receptor mediated gene activation, in an effort to identify down-stream genomic targets of this well-known, glucocorticoid induced, pro-resolution factor.
Downstream gene activation of the receptor ALX by the agonist annexin A1.
No sample metadata fields
View SamplesmiR-372-3p target identification mRNA level Overall design: Differential expression analysis 30h post transfection with miR-372-3p mimics
microRNAs with AAGUGC seed motif constitute an integral part of an oncogenic signaling network.
Specimen part, Cell line, Treatment, Subject
View SamplesY-chromosome aneuploidy strains were generated for 2 distinct Y chromosomes (Ycongo and Yohio), and expression profile analyzed by RNA-seq. Overall design: CONTRAST 1: X^X (control) vs X^XYohio; CONTRAST 2: X^X (control) vs X^XYcongo; CONTRAST 3: X^Y (control) vs X^YYohio; CONTRAST 4: X^Y (control) vs X^YYcongo.
The Y Chromosome Modulates Splicing and Sex-Biased Intron Retention Rates in <i>Drosophila</i>.
Sex, Specimen part, Subject
View SamplesMammalian genomes are organized into megabase-scale topologically associated domains (TADs) that have been proposed to represent large regulatory units. Here we demonstrate that disruption of TADs can cause rewiring of long-range regulatory architecture and result in pathogenic phenotypes. We show that distinct human limb malformations are caused by deletions, inversions, or duplications altering the structure of the TAD-spanning WNT6/IHH/EPHA4/PAX3 locus. Using CRISPR/Cas genome editing, we generated mice with corresponding rearrangements. Both in mouse limb tissue and patient-derived fibroblasts, disease-relevant structural changes cause ectopic interactions between promoters and non-coding DNA, and a cluster of limb enhancers normally associated with Epha4 is misplaced relative to TAD boundaries and drives ectopic limb expression of another gene in the locus. Our results demonstrate the functional importance of TADs for orchestrating gene expression via genome architecture and indicate criteria for predicting the pathogenicity of human structural variants, particularly in non-coding regions of the human genome. Overall design: RNA-seq profile of developing distal limbs of mutants and WT animals at E11.5
Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions.
No sample metadata fields
View SamplesGenome-scale methods have identified subchromosomal structures so-called topologically associated domains (TADs) that subdivide the genome into discrete regulatory units, establish with their target genes. By re-engineering human duplications at the SOX9 locus in mice combined with 4C-seq and Capture Hi-C experiments, we show that genomic duplications can result in the formation of novel chromatin domains (neo-TADs) and that this process determines their molecular pathology. Overall design: RNA-seq of embryonic limb buds for WT and mutant animals carrying structural variations at the Sox9/Kcnj locus.
Formation of new chromatin domains determines pathogenicity of genomic duplications.
Specimen part, Subject
View SamplesCaspases are cysteine-proteases with key roles in the execution phase of apoptosis. Additional cellular activities, unrelated to cell death seem to be influenced by these enzymes. Identification of genes co-regulated with caspases could help to ascertain new biological roles for these proteases.To identify genes and pathways under the influence of caspase-2 we silenced its expression in U87MG glioblastoma cell line. Transcriptional expression profiles of cells transfected with caspase-2 siRNA or control siRNA were compared.
Transcriptomic analysis unveils correlations between regulative apoptotic caspases and genes of cholesterol homeostasis in human brain.
Cell line, Treatment
View Samples7d-old WT ler seedlings were submitted to 12h of non-stress (air) or hypoxia-stress treatment under low light conditions (45 uM m-2 s-2), and Total and Large Polysome RNA from both treatments were extracted and hybridized against Affymetrix genome chips. Values were used to evaluate changes in transcript abundance and transcript association with large polysomal complexes.
Genome-wide analysis of transcript abundance and translation in Arabidopsis seedlings subjected to oxygen deprivation.
No sample metadata fields
View SamplesMalignant gliomas constitute one of the most significant areas of unmet medical need, due to the invariable failure of surgical eradication and their marked molecular heterogeneity. Accumulating evidence has revealed a critical contribution by the Polycomb axis of epigenetic repression. However, a coherent understanding of the regulatory networks affected by Polycomb during gliomagenesis is still lacking. Here we integrate transcriptomic and epigenomic analyses to define Polycomb-dependent networks that promote gliomagenesis, validating them both in two independent mouse models and in a large cohort of human samples. We found that Polycomb dysregulation in gliomagenesis affects transcriptional networks associated to invasiveness and de-differentiation. The dissection of these networks uncovers Zfp423 as a crtitical Polycomb-dependent transcription factor whose silencing negatively impacts survival. The anti-gliomagenic activity of Zfp423 requires interaction with the SMAD proteins within the BMP signaling pathway, pointing to a novel synergic circuit through which Polycomb inhibits BMP signaling. Overall design: Transcriptomic analysis of two different stages of gliomagenesis
Polycomb dysregulation in gliomagenesis targets a Zfp423-dependent differentiation network.
Specimen part, Cell line, Subject
View SamplesMutations in the gene encoding laminin a2 chain cause congenital muscular dystrophy, MDC1A. In skeletal muscle, laminin a2 chain binds at least two receptor complexes; the dystrophin-glycoprotein complex and integrin a7b1. To gain insight into the molecular mechanisms underlying this disorder, we performed gene expression profiling of laminin a2 chain deficient mouse limb muscle. One of the down-regulated genes encodes a protein called calcium and integrin binding protein 2 (Cib2) whose expression and function is unknown. However, the closely related Cib1 has been reported to bind integrin aIIb and may be involved in outside-in-signaling in platelets. Since Cib2 might be a novel integrin a7b1 binding protein in muscle, we have studied Cib2 expression in the developing and adult mouse. Cib2 mRNA is mainly expressed in the developing central nervous system and in developing and adult skeletal muscle. In skeletal muscle Cib2 colocalizes with integrin a7B subunit at the sarcolemma and at the neuromuscular- and myotendinous junctions. Finally, we demonstrate that Cib2 is a calcium binding protein that interacts with integrin a7Bb1D. Thus, our data suggest a role for Cib2 as a cytoplasmic effector of integrin a7Bb1D signaling in skeletal muscle
Cib2 binds integrin alpha7Bbeta1D and is reduced in laminin alpha2 chain-deficient muscular dystrophy.
No sample metadata fields
View SamplesGene expression analysis of 7d-old Arabidopsis seedlings exposed to short term (2 h) hypoxia, long term (9 h) hypoxia, and 1 h reoxygenation after long term (9 h) hypoxia to evaluate the regulation of gene expression at the level of translation.
Selective mRNA translation coordinates energetic and metabolic adjustments to cellular oxygen deprivation and reoxygenation in Arabidopsis thaliana.
Age
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