Structural Basis for Cytoplasmic Factors Required for Integrator and CPSF Function
Ontology highlight
ABSTRACT: The object of this study (or experiment) was to determine the impact of BRAT1 depletion on the transcriptome during differentiation into neuroprogenitor cells. Two control and two BRAT1 knockout H7-human ESC lines were differentiated for 14 days, total RNA isolated and polyA enriched Click-seq libraries generated. Broad transcriptional misregulation was observed between differentiated knockout and control lines. Specifically, the precocious upregulation of several neurogenesis-driving transcription factors indicates the mistiming of differentiation.
Project description:We previously reported that Asunder (ASUN) is essential for recruitment of dynein motors to the nuclear envelope (NE) and nucleus-centrosome coupling at the onset of cell division in cultured human cells and Drosophila spermatocytes, although the mechanisms underlying this regulation remain unknown. We also identified ASUN as a functional component of Integrator (INT), a multisubunit complex required for 3'-end processing of small nuclear RNAs. We now provide evidence that ASUN acts in the nucleus in concert with other INT components to mediate recruitment of dynein to the NE. Knockdown of other individual INT subunits in HeLa cells recapitulates the loss of perinuclear dynein in ASUN-small interfering RNA cells. Forced localization of ASUN to the cytoplasm via mutation of its nuclear localization sequence blocks its capacity to restore perinuclear dynein in both cultured human cells lacking ASUN and Drosophila asun spermatocytes. In addition, the levels of several INT subunits are reduced at G2/M when dynein is recruited to the NE, suggesting that INT does not directly mediate this step. Taken together, our data support a model in which a nuclear INT complex promotes recruitment of cytoplasmic dynein to the NE, possibly via a mechanism involving RNA processing.
Project description:The object of this study was to investigate the effect of elevated glucose concentrations (15 and 25 mM glucose) on gene expression in undifferentiated and adipogenic differentiated ASCs.
Project description:UnlabelledTwo new tools on the UCSC Genome Browser web site provide improved ways of combining information from multiple datasets, optionally including the user's own custom track data and/or data from track hubs. The Data Integrator combines columns from multiple data tracks, showing all items from the first track along with overlapping items from the other tracks. The Variant Annotation Integrator is tailored to adding functional annotations to variant calls; it offers a more restricted set of underlying data tracks but adds predictions of each variant's consequences for any overlapping or nearby gene transcript. When available, it optionally adds additional annotations including effect prediction scores from dbNSFP for missense mutations, ENCODE regulatory summary tracks and conservation scores.Availability and implementationThe web tools are freely available at http://genome.ucsc.edu/ and the underlying database is available for download at http://hgdownload.cse.ucsc.edu/ The software (written in C and Javascript) is available from https://genome-store.ucsc.edu/ and is freely available for academic and non-profit usage; commercial users must obtain a license.Contactangie@soe.ucsc.eduSupplementary informationSupplementary data are available at Bioinformatics online.
Project description:Analysis of differentiated Caco-2 intestinal epithelial cell line cocultured with probiotics L. acidophilus NCFM™, B. lactis 420, L. salivarius Ls-33 bacterial cells or treated with cell-free supernatant, and with E. coli O157:H7 cell-free supernatant. Lactobacillus and Bifidobacterium are important genera suggested to be beneficial for human health and E. coli O157:H7 is a pathogen causing hemorrhagic colitis and hemolytic uremic syndrome. Results provide insight into the mechanisms underlying the beneficial effects of probiotics on intestinal epithelial cells and a comparison to pathogenic E. coli.
Project description:Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Although macrophages are known to promote both the initiation and resolution of lung injury in reversible PF, it remains unclear how macrophages contribute to the progression of chronic PF. The object of this study was to investigate the role of inflammatory monocyte-derived macrophages (MMs) in the transcriptomic signatures of the lung tissue cells from murine progressive PF. We collected CD45-negative lung tissue cells from silica-treated CCR2 knockout and WT mice on days 28, 40 and untreated mice on day 0 post-aspiration and performed global transcriptome analyses using microarray. Data were analyzed by fuzzy c-means or CLICK clustering, gene set enrichment analysis, and network analyses. Global transcriptome analyses revealed that MM deficiency potentiated changes in gene-expression in tissue cells, closely matching trends seen in human chronic PF. Regulatory network analysis of transcriptome data suggested that MM-derived factors, such as tumor necrosis factor-α, were involved in the suppression of tissue remodeling-related gene expression. Overall, these results demonstrate that MMs suppress tissue cell responses and associated pathology in progressive PF.
Project description:Knockdown of PRDM2 led to precocious differentiation. To understand the molecular basis for this phenotype, we performed microaary analysis of 28hr differentiated myoblasts. Genes differentially regulated by PRDM2 knock down were reveraled by microarray analysis using affymetrix mouse chips.
2015-06-30 | GSE58673 | GEO
Project description:Comparison of precocious and non-precocious salmon
Project description:Abstract: Glucose serves as a universal energy currency in living organisms, however, its potential non-energetic biomolecular functions are less well defined. Glucose was among the most increased analytes among >14,000 assessed across epidermal differentiation, an elevation verified in tissue engineered with fluorescent glucose sensors and also observed in differentiating cells from other tissues. Free glucose accumulation, but not its increased metabolism, was essential for epidermal differentiation and required GLUT1, GLUT3, and SLC5A1 transporters. Glucose affinity chromatography and azido-glucose click chemistry revealed direct glucose binding to a variety of regulatory proteins, including the IRF6 transcription factor (TF), whose epidermal knockout confirmed its requirement in glucose-dependent differentiation. Glucose binding mediated IRF6 dimerization, DNA affinity, and genomic targeting. The IRF6R84C mutant found in poorly differentiated cancers was unable to bind glucose. These data demonstrate a non-energetic role for glucose in modulating protein multimerization to control genome dynamics. Purpose: To determine the impact of glucose modulation on chromatin accessibility during keratinocyte differentiation and the impact of IRF6 loss on chromatin accessibilty in differentiated keratincoytes
Project description:The objective was to compare gene expression in salmon precocious and non-precocious parr brain tissue. Eight microarray hybridisations were carried out in total as part of this design. To compare brain samples total RNA from 10 individual brains (dissected of hypothalamus and pituitary) of precocious fish and 10 brains of non-precocious fish were pooled to give two pools each of five precocious (PA and PB) and non-precocious (NPA and NPB) brains. Each pool of precocious brains was compared in a dye swap experiment with each pool of non-precocious brains.