Search results for "Gene expression."
showing 10 items of 4076 documents
The POT1 gene for yeast peroxisomal thiolase is subject to three different mechanisms of regulation
1992
The Saccharomyces cerevisiae POT1 gene is, as are other yeast peroxisomal protein genes, inducible by fatty acids and repressible by glucose. We have now found that it is also induced during the stationary phase of the culture. To investigate these three regulatory circuits, we have studied the mRNA levels of regulatory mutants as well as the changes in chromatin structure upon gene activation. We conclude that the regulation of transcriptional activity in glucose repression, oleate induction, and stationary phase induction follow different molecular mechanisms. We suggest that this multiplicity of regulatory mechanisms may represent a general rule for the yeast peroxisomal protein genes.
Transcriptional Regulation of Human CYP3A4 Basal Expression by CCAAT Enhancer-Binding Protein α and Hepatocyte Nuclear Factor-3γ
2003
Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of more than 50% of currently used therapeutic drugs, yet the mechanisms that control CYP3A4 basal expression in liver are poorly understood. Several putative binding sites for CCAAT/enhancer-binding protein (C/EBP) and hepatic nuclear factor 3 (HNF-3) were found by computer analysis in CYP3A4 promoter. The use of reporter gene assays, electrophoretic mobility shift assays, and site-directed mutagenesis revealed that one proximal and two distal C/EBP alpha binding sites are essential sites for the trans-activation of CYP3A4 promoter. No trans-activation was found in similar reporter gene experiments with a HNF-3 gamma expression vec…
Hypoxia-inducible factor 1Α may regulate the commitment of mesenchymal stromal cells toward angio-osteogenesis by mirna-675-5P
2017
Abstract Background aims During bone formation, angiogenesis and osteogenesis are regulated by hypoxia, which is able to induce blood vessel formation, as well as recruit and differentiate human mesenchymal stromal cells (hMSCs). The molecular mechanisms involved in HIF-1α response and hMSC differentiation during bone formation are still unclear. This study aimed to investigate the synergistic role of hypoxia and hypoxia-mimetic microRNA miR-675-5p in angiogenesis response and osteo-chondroblast commitment of hMSCs. Methods By using a suitable in vitro cell model of hMSCs (maintained in hypoxia or normoxia), the role of HIF-1α and miR-675-5p in angiogenesis and osteogenesis coupling was inv…
The modulator is a constitutive enhancer of a developmentally regulated sea urchin histone H2A gene.
2002
Going back to the late 1970s and early 1980s, we trace the Xenopus oocyte microinjection experiments that led to the emergence of the concept of “modulator”. The finding that the modulator could transactivate transcription from far upstream and in either orientation suggested that a new genetic element, different from the classical prokaryotic promoter sequences, had been discovered. This particular enhancer transactivates transcription of the sea urchin early (α) histone H2A gene which is regulated in early sea urchin development. We summarise the data from sea urchin microinjection experiments that confirm and extend the results obtained with Xenopus oocytes. We conclude that the H2A enha…
Cadmium as a transcriptional modulator in human cells
2010
Cadmium (Cd) is an underground mineral widely used in the steel industry, in plastics, and as a component of batteries. It is an industrial and environmental pollutant released as an air contaminant from fertilizers and, more prominently, in the form of wastewater. Food, drinking water, and, mainly, inhalation of smoke from cigarettes are sources of daily exposure of humans to the heavy metal. Although Cd has no known useful function for humans as well as other organisms, it appears to evoke in cells a number of responses that involve not only death signaling but also protective reactions against the toxicity. This finding prompted a number of experimental studies aimed to elucidate the cel…
The Wilms' tumor suppressor gene (wt1) product regulates Dax-1 gene expression during gonadal differentiation.
1999
Gonadal differentiation is dependent upon a molecular cascade responsible for ovarian or testicular development from the bipotential gonadal ridge. Genetic analysis has implicated a number of gene products essential for this process, which include Sry, WT1, SF-1, and DAX-1. We have sought to better define the role of WT1 in this process by identifying downstream targets of WT1 during normal gonadal development. We have noticed that in the developing murine gonadal ridge, wt1 expression precedes expression of Dax-1, a nuclear receptor gene. We document here that the spatial distribution profiles of both proteins in the developing gonad overlap. We also demonstrate that WT1 can activate the D…
Physiological activation of the IgH 3' enhancer in B lineage cells is not blocked by Pax-5.
1996
The mouse 3' enhancer contains a high-affinity binding site for the paired box protein Pax-5. Here, we demonstrate by genomic footprinting that the rat 3' enhancer contains a low-affinity binding site for Pax-5, which is occupied in activated splenic B cells. Thus, binding of Pax-5 to the IgH 3' enhancer appears to be evolutionarily conserved in rodents. Analysis of Pax-5 expression in primary B cells demonstrates that Pax-5 remains expressed after 4 days of lipopolysaccharide (LPS) induction, but is down-regulated in 5-day stimulated cells. Similarly, the expression of Pax-5 is down-regulated in vivo in activated large splenocytes, in contrast to small resting cells. Multimerization of the…
A differential role of CREB phosphorylation in cAMP-inducible gene expression in the rat pineal
2000
In the rat pineal gland cAMP mediates nocturnal induction of the enzyme arylalkylamine N-acetyltransferase (AA-NAT) as well as of transcription factors such as inducible cAMP early repressor (ICER), Fos-related antigen-2 (Fra-2) and JunB. Cyclic AMP stimulates the phosphorylation of the DNA binding protein cAMP response element binding protein (CREB). While cAMP-induced CREB phosphorylation appears to be a prerequisite for AA-NAT and ICER gene expression, it is not known whether CREB phosphorylation accounts for the full cAMP response of the two genes. Furthermore, the significance of CREB phosphorylation in cAMP-activated Fra-2 and JunB transcription is unknown. In the present in vitro stu…
Synthetic retinoids dissociate coactivator binding from corepressor release.
2002
The ligand-activated retinoid receptors RXR and RAR control development, homeostasis and disease by regulating transcription of retinoic acid (RA) responsive target genes or crosstalk with other signalling pathways. According to the current model ligand-binding triggers an exchange between corepressor- and coactivator-complexes that inhibit or potentiate transcription by deacetylating and acetylating nucleosomal histones, respectively. Additional cofactors may modify the transcriptional regulatory process by linking liganded retinoid receptors to structural components of chromatin or protein degradation. The desire to specifically influence defined events in RA-signalling, while others are …
The yopJ locus is required for Yersinia-mediated inhibition of NF-kappaB activation and cytokine expression: YopJ contains a eukaryotic SH2-like doma…
1998
Upon exposure to bacteria, eukaryotic cells activate signalling pathways that result in the increased expression of several defence-related genes. Here, we report that the yopJ locus of the enteropathogen Yersinia pseudotuberculosis encodes a protein that inhibits the activation of NF-kappaB transcription factors by a mechanism(s), which prevents the phosphorylation and subsequent degradation of the inhibitor protein IkappaB. Consequently, eukaryotic cells infected with YopJ-expressing Yersinia become impaired in NF-kappaB-dependent cytokine expression. In addition, the blockage of inducible cytokine production coincides with yopJ-dependent induction of apoptosis. Interestingly, the YopJ pr…