Search results for "Transcriptional activation"
showing 10 items of 102 documents
Patchwork Pattern of Transcriptional Reactivation in the Lungs Indicates Sequential Checkpoints in the Transition from Murine Cytomegalovirus Latency…
1999
The lungs are a relevant organ site of primary and recurrent human cytomegalovirus (hCMV) disease (for overviews, see references 21, 22, 31, 34, 39, and 44). Murine CMV (mCMV) can serve us as a model for studying CMV pneumonia in acute infection (6, 27, 33, 37) as well as for studying viral latency, reactivation, and recurrence in the lungs (2, 17, 18, 42, 43). We have shown recently that transcription from the major immediate-early (MIE) transcription unit ie1-ie3 (hereafter referred to as ie1/3), which is driven by a strong MIE promoter-enhancer (MIEPE) (3), occurs during pulmonary latency of mCMV but fails to initiate the productive cycle (17). Notably, the paralogous MIEPE of hCMV can f…
Of mice and models: improved animal models for biomedical research.
2002
The ability to engineer the mouse genome has profoundly transformed biomedical research. During the last decade, conventional transgenic and gene knockout technologies have become invaluable experimental tools for modeling genetic disorders, assigning functions to genes, evaluating drugs and toxins, and by and large helping to answer fundamental questions in basic and applied research. In addition, the growing demand for more sophisticated murine models has also become increasingly evident. Good state-of-principle knowledge about the enormous potential of second-generation conditional mouse technology will be beneficial for any researcher interested in using these experimental tools. In thi…
Insulin-dependent leptin expression in breast cancer cells.
2008
Abstract Pathologic conditions associated with hyperinsulinemia, such as obesity, metabolic syndrome, and diabetes, seem to increase the risk of breast cancer. Here, we studied molecular mechanisms by which insulin activates the expression of leptin, an obesity hormone that has been shown to promote breast cancer progression in an autocrine or paracrine way. Using MDA-MB-231 breast cancer cells, we found that (a) insulin stimulated leptin mRNA and protein expression, which was associated with increased activation of the leptin gene promoter; (b) insulin increased nuclear accumulation of transcription factors hypoxia inducible factor (HIF)-1α and Sp1 and their loading on the leptin promoter;…
Leptin/HER2 crosstalk in breast cancer: in vitro study and preliminary in vivo analysis.
2008
Abstract Background Obesity in postmenopausal women is associated with increased breast cancer risk, development of more aggressive tumors and resistance to certain anti-breast cancer treatments. Some of these effects might be mediated by obesity hormone leptin, acting independently or modulating other signaling pathways. Here we focused on the link between leptin and HER2. We tested if HER2 and the leptin receptor (ObR) can be coexpressed in breast cancer cell models, whether these two receptors can physically interact, and whether leptin can transactivate HER2. Next, we studied if leptin/ObR can coexist with HER2 in breast cancer tissues, and if presence of these two systems correlates wi…
Deletion of organic cation transporter Oct3 promotes hepatic fibrosis via upregulation of TGFβ
2019
Organic cation transporters (OCT) are responsible for the intracellular uptake and detoxification of a broad spectrum of endogenous and exogenous substrates. OCTs are downregulated in cholestasis, fibrosis, and hepatocellular carcinoma, but the underlying molecular mechanisms and downstream effects of OCT deletion are unknown. Oct3-knockout ( Oct3−/−; FVB.Slc22a3tm10pb) and wild-type (WT; FVB) mice were subject to escalating doses of carbon tetrachloride (CCl4) or thioacetamide (TAA) for 6 wk to induce advanced parenchymal liver fibrosis. Secondary biliary fibrosis was generated by bile duct ligation. Liver fibrosis was assessed by hydroxyproline determination, quantitative Sirius red morp…
A functional analysis of ACP-20, an adult-specific cuticular protein gene from the beetle Tenebrio. Role of an intronic sequence in transcriptional a…
2004
0962-1075 (Print) Comparative Study Journal Article Research Support, Non-U.S. Gov't; A gene encoding the adult cuticular protein ACP-20 was isolated in Tenebrio. It consists of three exons interspersed by two introns, intron 1 interrupting the signal peptide. To understand the regulatory mechanisms of ACP-20 expression, ACP-20 promoter-luciferase reporter gene constructs were transfected into cultured pharate adult wing epidermis. Transfection assays needed the presence of 20-hydroxyecdysone, confirming that ACP-20 is up-regulated by ecdysteroids. Analysis of 5' deletion constructs revealed that three regions are necessary for high levels of transcription. Interaction experiments between i…
In vivo GSH depletion induces c-myc expression by modulation of chromatin protein complexes.
2009
Abstract We hypothesize that glutathione (GSH) fluctuations could have a prominent role in the modulation of c-myc expression through a mechanism affecting chromatin remodeling complexes. This could lead to an open chromatin structure accessible to transcription factors. We studied the in vivo effect of GSH depletion on these complexes bound to the c-myc promoter in the liver of l-buthionine-(S,R)-sulfoximine (BSO)-treated rats. Using chromatin immunoprecipitation we found that 3 h after BSO treatment the repressing complexes Id2 and Sin3A (part of a histone–deacetylase complex) were released from the c-myc promoter. STAT3 was phosphorylated and associated with its coactivator p300 with int…
Human somatic cells subjected to genetic induction with six germ line-related factors display meiotic germ cell-like features
2016
AbstractThe in vitro derivation of human germ cells has attracted interest in the last years, but their direct conversion from human somatic cells has not yet been reported. Here we tested the ability of human male somatic cells to directly convert into a meiotic germ cell-like phenotype by inducing them with a combination of selected key germ cell developmental factors. We started with a pool of 12 candidates that were reduced to 6, demonstrating that ectopic expression of the germ line-related genes PRDM1, PRDM14, LIN28A, DAZL, VASA and SYCP3 induced direct conversion of somatic cells (hFSK (46, XY) and hMSC (46, XY)) into a germ cell-like phenotype in vitro. Induced germ cell-like cells …
Downregulation of β2-microglobulin in human cord blood somatic stem cells after transplantation into livers of SCID-mice: an escape mechanism of stem…
2002
Adherently growing, non-hematopoietic somatic stem cells isolated from human cord blood were stained with the fluorescent dye PKH26 and transplanted into livers of SCID-mice to examine a possible cell fate transition. Already 7 days after transplantation stem cells were well integrated into the liver tissue. Human albumin that was not expressed by the stem cells before transplantation was detectable in the host's livers after injection of cord blood stem cells. Human alpha1-antitrypsin was detectable in stem cells already before transplantation and remained positive in the mouse liver. The most interesting observation in this study was the downregulation of human beta2-microglobulin (beta2M…
Chronic lithium salt treatment reduces CRE/CREB-directed gene transcription and reverses its upregulation by chronic psychosocial stress in transgeni…
2007
The molecular mechanism of action of the mood stabilizer lithium is assumed to involve changes in gene expression leading to neuronal adaptation. The transcription factor CREB (cAMP-responsive element binding protein) regulates the expression of many genes and has been implicated in important brain functions and the action of psychogenic agents. We here investigated the effect of lithium on cAMP-responsive element (CRE)/CREB-mediated gene transcription in the brain, using transgenic reporter mice that express the luciferase reporter gene under the control of four copies of the rat somatostatin gene promoter CRE. Chronic (21 days) but not acute (24 h) treatment with lithium (7.5 mmol/kg) sig…