Search results for "Models"
showing 10 items of 8211 documents
The stable repression of mesenchymal program is required for hepatocyte identity: A novel role for hepatocyte nuclear factor 4α
2011
The concept that cellular terminal differentiation is stably maintained once development is complete has been questioned by numerous observations showing that differentiated epithelium may undergo an epithelial-to-mesenchymal transition (EMT) program. EMT and the reverse process, mesenchymal-to-epithelial transition (MET), are typical events of development, tissue repair, and tumor progression. In this study, we aimed to clarify the molecular mechanisms underlying these phenotypic conversions in hepatocytes. Hepatocyte nuclear factor 4α (HNF4α) was overexpressed in different hepatocyte cell lines and the resulting gene expression profile was determined by real-time quantitative polymerase…
A complete set of nascent transcription rates for yeast genes
2010
The amount of mRNA in a cell is the result of two opposite reactions: transcription and mRNA degradation. These reactions are governed by kinetics laws, and the most regulated step for many genes is the transcription rate. The transcription rate, which is assumed to be exercised mainly at the RNA polymerase recruitment level, can be calculated using the RNA polymerase densities determined either by run-on or immunoprecipitation using specific antibodies. The yeast Saccharomyces cerevisiae is the ideal model organism to generate a complete set of nascent transcription rates that will prove useful for many gene regulation studies. By combining genomic data from both the GRO (Genomic Run-on) a…
Chromatin structure of the yeast FBP1 gene: transcription-dependent changes in the regulatory and coding regions.
1993
We have studied the chromatin structure of the Saccharomyces cerevisiae FBP1 gene, which codes for fructose-1,6-bisphosphatase. A strong, constitutive, DNase I, micrococcal nuclease and S1 nuclease hypersensitive site is present close to the 3′ end of the coding region. In the repressed state, positioned nucleosomes exist around this site, and subtle changes occur in this nucleosomal organization upon derepression. A DNase I hypersensitive region is located within the promoter between positions −540 and −400 and it extends towards the gene in the derepressed state, leading to an alteration of nucleosomal positioning. Psoralen crosslinking of chromatin, which is used for the first time to st…
Transcriptional Activity and Nuclear Localization of Cabut, the Drosophila Ortholog of Vertebrate TGF-β-Inducible Early-Response Gene (TIEG) Proteins
2011
Background Cabut (Cbt) is a C2H2-class zinc finger transcription factor involved in embryonic dorsal closure, epithelial regeneration and other developmental processes in Drosophila melanogaster. Cbt orthologs have been identified in other Drosophila species and insects as well as in vertebrates. Indeed, Cbt is the Drosophila ortholog of the group of vertebrate proteins encoded by the TGF-s-inducible early-response genes (TIEGs), which belong to Sp1-like/Kruppel-like family of transcription factors. Several functional domains involved in transcriptional control and subcellular localization have been identified in the vertebrate TIEGs. However, little is known of whether these domains and fu…
Rapid nucleus-scale reorganization of chromatin in neurons enables transcriptional adaptation for memory consolidation
2020
AbstractThe interphase nucleus is functionally organized in active and repressed territories defining the transcriptional status of the cell. However, it remains poorly understood how the nuclear architecture of neurons adapts in response to behaviorally relevant stimuli that trigger fast alterations in gene expression patterns. Imaging of fluorescently tagged nucleosomes revealed that pharmacological manipulation of neuronal activity in vitro and auditory cued fear conditioning in vivo induce nucleus-scale restructuring of chromatin within minutes. Furthermore, the acquisition of auditory fear memory is impaired after infusion of a drug into auditory cortex which blocks chromatin reorganiz…
Expression levels of a filament-specific transcriptional regulator are sufficient to determine Candida albicans morphology and virulence
2009
Candida albicans , the major human fungal pathogen, undergoes a reversible morphological transition from single yeast cells to pseudohyphal and hyphal filaments (elongated cells attached end-to-end). Because typical C. albicans infections contain a mixture of these morphologies it has, for many years, been difficult to assess the relative contribution of each form to virulence. In addition, the regulatory mechanisms that determine growth in pseudohyphal and hyphal morphologies are largely unknown. To address these questions we have generated a C. albicans strain that can be genetically manipulated to grow completely in the hyphal form under non-filament-inducing conditions in vitro. This w…
RNA memory model: a RNA-mediated transcriptional activation mechanism involved in cell identity.
2010
Position-effect variegation (PEV) was discovered in Drosophila melanogaster in 1930 in a study of X-ray-induced chromosomal rearrangements. If a rearrangement places euchromatic genes adjacent to a region of centromeric heterochromatin, it gives a variegated phenotype that results from the random inactivation of genes by heterochromatin spreading from the breakpoint. After the establishment, the inactivation is henceforth clonally inherited. The vast majority of these modifiers were originally isolated in Drosophila as dominant mutations that suppressed or enhanced the variegation caused by a variegating white allele called white-mottled 4 (wm4). A large number of modifier genes alter PEV p…
CD8 T Cells Control Cytomegalovirus Latency by Epitope-Specific Sensing of Transcriptional Reactivation
2006
ABSTRACT During murine cytomegalovirus (mCMV) latency in the lungs, most of the viral genomes are transcriptionally silent at the major immediate-early locus, but rare and stochastic episodes of desilencing lead to the expression of IE1 transcripts. This low-frequency but perpetual expression is accompanied by an activation of lung-resident effector-memory CD8 T cells specific for the antigenic peptide 168-YPHFMPTNL-176, which is derivedfrom the IE1 protein. These molecular and immunological findings were combined in the “silencing/desilencing and immune sensing hypothesis” of cytomegalovirus latency and reactivation. This hypothesis proposes that IE1 gene expression proceeds to cell surfac…
Regulation of the tumor marker Fascin by the viral oncoprotein Tax of human T-cell leukemia virus type 1 (HTLV-1) depends on promoter activation and …
2015
AbstractAdult T-cell leukemia/lymphoma is a highly infiltrative neoplasia of CD4+ T-lymphocytes that occurs in about 5% of carriers infected with the deltaretrovirus human T-cell leukemia virus type 1 (HTLV-1). The viral oncoprotein Tax perturbs cellular signaling pathways leading to upregulation of host cell factors, amongst them the actin-bundling protein Fascin, an invasion marker of several types of cancer. However, transcriptional regulation of Fascin by Tax is poorly understood. In this study, we identified a triple mode of transcriptional induction of Fascin by Tax, which requires (1) NF-κB-dependent promoter activation, (2) a Tax-responsive region in the Fascin promoter, and (3) a p…
Increased AICD generation does not result in increased nuclear translocation or activation of target gene transcription.
2008
A sequence of amyloid precursor protein (APP) cleavages culminates in the sequential release of the APP intracellular domain (AICD) and the amyloid beta peptide (Abeta) and/or p3 fragment. One of the environmental factors favouring the accumulation of AICD appears to be a rise in intracellular pH. Here we further identified the metabolism and subcellular localization of artificially expressed constructs under such conditions. We also co-examined the mechanistic lead up to the AICD accumulation and explored possible significances for its increased expression. We found that most of the AICD generated under pH neutralized conditions is likely cleaved from C83. While the AICD surplus was unable…