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Results for “Promoter dynamics”

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At least 163 records · Page 9Linked to original sources
PubMed1999

[Dynamic changes of basal core promoter and pre-core mutants of hepatitis B virus in patients with chronic hepatitis B virus infection].

OBJECTIVES: To clarify the association of hepatitis B virus mutants in basal core gene promoter and pre-c region with serum HBeAg state and persistent HBV infection. METHODS: 32 patients, who infected with hepatitis B virus and suffered from several exacerbation during the course of this disease, were followed up for an average of 20.8 months. Using two mis-matched primers to amplify BCP and pre-c gene fragments, in combination with restricted fragment length polymorphism assay, we studied the presence of these two mutants(nt 1762A-->T, 1764G-->A and nt1896G-->A) in 105 serum samples. Direct sequencing was performed on 15 patients' serial samples to identify the efficiency of these rapid and simple methods and other variations in these regions. RESULTS: The presence of these two kinds of mutants increased during the following-up, (62.5% > 46.9%; 31.3% > 12.5%). In most cases, two mutants prevailed and finally displaced the wild type virus; the serology of HBeAg was affected predominantly by the ratio of BCP mutant to wild type. CONCLUSION: BCP and pre-c mutants emerged in the course of chronic infection and were selected positively by the inflammation activity. The serological conditions of HBeAg were changed when the predominant situations of these two mutants were established. The survival of these two mutants implied that mutations in these two regions may contribute to the persistent infection of hepatitis B virus.

Adolescent↗
PubMed2003

2003 update on the Hypertension Initiative of South Carolina. Bringing South Carolina from "worst to first" in cardiovascular health.

Hypertension and its related comorbidities continue to drain South Carolina of approximately $9 billion dollars a year in direct medical costs and indirectly through lost productivity. Improving control rates of blood pressure and associated cardiovascular risk factors in the primary care physician's office is a fundamental and crucial step to decrease the very high incidence of stroke and cardiorenal diseases. By monitoring prescribing patterns through the Initiatives' data feedback program, providing evidence-based management approaches through educational seminars, and by applying improved treatment protocols, physicians can have a profound impact on outcomes. The growing collaborative partnership spawned by the Hypertension Initiative now includes primary care providers, Hypertension Specialists in the local community, and the ASH Carolinas-Georgia Chapter. The growth and impact of the partnership is facilitated by a dynamic data auditing and feedback program that provides the basis for constructive change focused on optimizing cardiovascular risk factor control in patients across the State. By continuing to make progress in addressing the control of blood pressure and associated cardiovascular risk factors through a growing collaborative partnership with primary care providers statewide, South Carolina can move from worst to first in cardiovascular health. In the future, we hope to add a dynamic health promotion program to active disease management efforts. In the process, South Carolina can move from a leader in cardiovascular disease to a model of cardiovascular health.

Education, Medical, Continuing↗
PubMed1986

[Health education methodology: an attempt at classification].

Health education is a major tool in the implementation of any dynamic health promotion policy. In the author's view, its conventional role, the improvement of health by bringing about behavioural changes is today subject to controversy. He identifies five key approaches in health education: the traditional approach, characterized by three features: the didactic provision of information, the use of fear as an educational technique, and the appeal to the individual's sense of responsibility for his own health. the media approach, which uses marketing methods to promote health, with a tendency to resort to positive humorous messages. the socio-political approach, which questions the very purpose of health education. According to those who hold this view, wide-scale educational campaigns would only increase social and health inequalities and would be quite ineffective in fighting the powerful economic interests that control most of our habits. The health educator's real role would be to raise the people's political awareness. the epidemiological approach, which aims at great soundness through precise planning by objectives. It is based on the so-called exact sciences such as epidemiology and its aim is to study needs and assess actions. It incorporates the classical concept according to which a change in knowledge leads to a change in behaviour and habits and thus induces health improvement. Its very elaborate character accounts for both its strength and its weakness. In fact, it takes little account of the complexity of the educational process. the community approach fills some of these gaps by stressing the participation of individuals and institutions at all programming levels. For this purpose, it uses techniques designed to ensure consensus. In conclusion, the author recommends that active research in health education be undertaken in order to clarify more adequately these approaches with a view to improving the effectiveness of preventive work.

Attitude to Health↗
PubMed1993

Kenyan university students' views on AIDS.

In view of the rapidly increasing number of AIDS cases reported in Kenya since 1984, a survey was conducted among Kenyatta University undergraduate students during October and November 1988 to gauge their knowledge, attitudes and practices with regard to the disease. A random sample of 344 individuals both men and women was interviewed. The results showed that almost everyone had heard about AIDS and the knowledge was spread evenly across gender. Although the students were able to identify the symptoms of a full blown AIDS victim, their knowledge on HIV was vague. Other findings were: that condoms were lowly rated as a strategy for minimizing the risk of contracting AIDS and the majority of the students attempted to reduce the chance of contracting the disease by having one sex partner. However, the students were apathetic about contracting the disease. In the event of becoming victims of AIDS, most of them indicated that they would not merely wait to die; instead they would commit suicide. In view of these findings, there is a case for educating this group on how to respond to the AIDS infection.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Muscarinic induction of synchronous population activity in the entorhinal cortex.

Oscillation and synchronization of neural activity is important in normal brain function but is also relevant to epileptogenesis. One of the most frequent forms of epilepsy originates in temporal lobe circuitry of which the entorhinal cortex (EC) is crucial. Because muscarinic receptor activation promotes oscillatory dynamics in EC neurons, we investigated in a brain slice preparation the effects of carbachol (CCh) on oscillatory population activity in the EC. We found that CCh produced epileptiform activity in EC, which according to field profile and current source density analysis was usually driven by layer V. In addition, localized CCh application and surgical isolation experiments demonstrated that EC layer II, but not layer III, can also independently generate synchronous population activity. Intracellular recordings from EC principal cells during epileptiform activity demonstrated large-amplitude, synaptically driven depolarizing events and bursts of action potentials synchronized to the field spikes. In layer II neurons, the depolarizing events had a multiphasic reversal potential that suggested concurrent glutamatergic and GABAergic synaptic input. Interestingly, although the epileptiform activity required activation of AMPA but not NMDA receptors, small-amplitude field spikes persisted during block of fast excitatory neurotransmission. These field spikes were correlated to large-amplitude IPSPs in layer II neurons, and both activities were abolished by GABAA-receptor antagonism. Thus, in response to muscarinic activation, pools of EC interneurons discharge synchronously by a mechanism not necessarily involving principal cell activation. Given the differential projection pattern of EC layers V and II toward the neocortex and hippocampus, respectively, their robust epileptogenic character may be of major importance in temporal lobe epilepsy.

Animals↗
PubMed2002

Dynamic behavior of transcription factors on a natural promoter in living cells.

Through the use of photobleaching techniques, we examined the dynamic interaction of three members of the transcription apparatus with a target promoter in living cells. The glucocorticoid receptor (GR) interacting protein 1 (GRIP-1) exhibits a half maximal time for fluorescent recovery (tau(R)) of 5 s, reflecting the same rapid exchange as observed for GR. In contrast, the large subunit (RPB1) of RNA polymerase II (pol II) required 13 min for complete fluorescence recovery, consistent with its function as a processive enzyme. We also observe a complex induction profile for the kinetics of GR-stimulated transcription. Our results indicate that GR and GRIP-1 as components of the activating complex are in a dynamic equilibrium with the promoter, and must return to the template many times during the course of transcriptional activation.

Animals↗
PubMed2006

Dynamic usage of transcription start sites within core promoters.

BACKGROUND: Mammalian promoters do not initiate transcription at single, well defined base pairs, but rather at multiple, alternative start sites spread across a region. We previously characterized the static structures of transcription start site usage within promoters at the base pair level, based on large-scale sequencing of transcript 5' ends. RESULTS: In the present study we begin to explore the internal dynamics of mammalian promoters, and demonstrate that start site selection within many mouse core promoters varies among tissues. We also show that this dynamic usage of start sites is associated with CpG islands, broad and multimodal promoter structures, and imprinting. CONCLUSION: Our results reveal a new level of biologic complexity within promoters--fine-scale regulation of transcription starting events at the base pair level. These events are likely to be related to epigenetic transcriptional regulation.

Animals↗
PubMed2026

Structures and dynamics of the major G-quadruplex in the human PDGFR-β gene promoter: insights into vacancy G-quadruplex formation.

Overexpression of PDGFR-β (platelet-derived growth factor receptor beta) kinase contributes to diverse human diseases, including cancers, cardiovascular disorders, and fibrosis. G-quadruplexes (G4s) formed in the PDGFR-β promoter act as transcriptional repressors and represent attractive therapeutic targets. We previously reported that the major G4-forming region of the PDGFR-β promoter adopts a unique broken-strand G4, whereas truncation of this sequence generates a vacancy G4 (vG4) that can be filled-in by external guanine analogs or metabolites and further stabilized by small molecules, suggesting a potential regulatory mechanism and opportunity for selective drug targeting. However, the relationship between broken-strand G4s and vG4s remains unclear. Here, we demonstrate that the PDGFR-β promoter sequence forms a dynamic equilibrium between two broken-strand G4 conformations that interconvert on the millisecond timescale, with vG4 serving as an intermediate. We determined the high-resolution NMR structures of these interconverting G4s, which share a conserved vG4 core but differ in their intramolecular guanine "fill-in." Both conformations feature a stabilizing G-G capping base pair unique to the PDGFR-β promoter. These findings elucidate the structural details of broken-strand PDGFR-β promoter G4s and the mechanism of vG4 formation, providing critical insights for selective drug targeting and establishing a framework for rational design of small molecules to modulate PDGFR-β transcription.

G-Quadruplexes↗
PubMed2003

Distinct transcriptional pathways regulate basal and activated major histocompatibility complex class I expression.

Transcription of major histocompatibility complex (MHC) class I genes is regulated by both tissue-specific (basal) and hormone/cytokine (activated) mechanisms. Although promoter-proximal regulatory elements have been characterized extensively, the role of the core promoter in mediating regulation has been largely undefined. We report here that the class I core promoter consists of distinct elements that are differentially utilized in basal and activated transcription pathways. These pathways recruit distinct transcription factor complexes to the core promoter elements and target distinct transcription initiation sites. Class I transcription initiates at four major sites within the core promoter and is clustered in two distinct regions: "upstream" (-14 and -18) and "downstream" (+12 and +1). Basal transcription initiates predominantly from the upstream start site region and is completely dependent upon the general transcription factor TAF1 (TAF(II)250). Activated transcription initiates predominantly from the downstream region and is TAF1 (TAF(II)250) independent. USF1 augments transcription initiating through the upstream start sites and is dependent on TAF1 (TAF(II)250), a finding consistent with its role in regulating basal class I transcription. In contrast, transcription activated by the interferon mediator CIITA is independent of TAF1 (TAF(II)250) and focuses initiation on the downstream start sites. Thus, basal and activated transcriptions of an MHC class I gene target distinct core promoter domains, nucleate distinct transcription initiation complexes and initiate at distinct sites within the promoter. We propose that transcription initiation at the core promoter is a dynamic process in which the mechanisms of core promoter function differ depending on the cellular environment.

Animals↗
PubMed2006

Periodic direct current does not promote wound closure in an in vitro dynamic model of cell migration.

BACKGROUND AND PURPOSE: A prevailing paradigm is that electrical fields can promote cell migration and tissue healing. To further validate this paradigm, we tested the hypothesis that periodic direct current (DC) can enhance wound closure using an in vitro dynamic model of cell migration. METHODS AND RESULTS: Layers of primary fibroblasts were wounded and treated with DC under various voltages. Repair area, cell velocity, and directionality as well as lamellipodium area were evaluated at different times. Direct current had no beneficial effect on cell migration. Moreover, prolonged stimulation under the highest voltage led to significant reduction in wound closure and cell velocity. The reduction of membrane protusions in stimulated cells may be associated with the deleterious effect of DC. DISCUSSION AND CONCLUSION: Contrary to the authors' expectations, they found that periodic DC did not promote wound closure, a finding that emphasizes the need to clarify the complex effects of electrical fields on migrating cells.

Animals↗
PubMed2005

HIV-1 clade promoters strongly influence spatial and temporal dynamics of viral replication in vivo.

Although the primary determinant of cell tropism is the interaction of viral envelope or capsid proteins with cellular receptors, other viral elements can strongly modulate viral replication. While the HIV-1 promoter is polymorphic for a variety of transcription factor binding sites, the impact of these polymorphisms on viral replication in vivo is not known. To address this issue, we engineered isogenic SIVmac239 chimeras harboring the core promoter/enhancer from HIV-1 clades B, C, and E. Here it is shown that the clade C and E core promoters/enhancers bear a noncanonical activator protein-1 (AP-1) binding site, absent from the corresponding clade B region. Relative ex vivo replication of chimeras was strongly dependent on the tissue culture system used. Notably, in thymic histocultures, replication of the clade C chimera was favored by IL-7 enrichment, which suggests that the clade C polymorphism in the AP-1 and NF-kappaB binding sites is involved. Simultaneous infection of rhesus macaques with the 3 chimeras revealed a strong predominance of the clade C chimera during primary infection. Thereafter, the B chimera dominated in all tissues. These data show that the clade C promoter is particularly adapted to sustain viral replication in primary viremia and that clade-specific promoter polymorphisms constitute a major determinant for viral replication.

Animals↗
PubMed2006

Chromatin dynamics and the evolution of alternate promoter states.

Eucaryotic gene transcriptional switches utilize changes both in the activity and composition of soluble transcription factor complexes, and epigenetic modifications to the chromatin template. Until recently, alternate states of promoter activity have been associated with the assembly of relatively stable multiprotein complexes on target genes, with transitions in the composition of these complexes occurring on the time scale of minutes or hours. The development of living cell techniques to characterize transcription factor function in real time has led to an alternate view of highly dynamic protein/template interactions. In addition, emerging evidence suggests that energy-dependent processes contribute significantly to the rapid movement of proteins in living cells, and to the exchange of sequence-specific DNA-binding proteins with regulatory elements. Potential mechanisms involved in the unexpectedly rapid flux of factor/template interactions are discussed in the context of a "return-to-template" model for transcription factor function.

Animals↗
PubMed2005

Osteo-Promoter Database (OPD) -- promoter analysis in skeletal cells.

BACKGROUND: Increasing our knowledge about the complex expression of genes in skeletal tissue will provide a better understanding of the physiology of skeletal cells. The study summarizes transcriptional regulation factors interacting and cooperating at promoter regions that regulate gene expression. Specifically, we analyzed A/T rich elements along the promoter sequences. DESCRIPTION: The Osteo-Promoter Database (OPD) is a collection of genes and promoters expressed in skeletal cells. We have compiled a new viewer, OPD, as unique database developed and created as an accessible tool for skeletal promoter sequences. OPD can navigate to identify genes specific to skeletal cDNA databases and promoter analysis sites. OPD offers exclusive access to facilitate a dynamic extraction of promoters' gene-specific analyses in skeletal tissue. The data on promoters included in OPD contains cloned promoters or predicted promoters that were analyzed by bioinformatics tools. OPD offers MAR-analysis, which allocates A/T rich elements along these promoter sequences. CONCLUSION: The analysis leads to a better insight of proteins that bind to DNA, regulate DNA, and function in chromatin remodeling. The OPD is a distinctive tool for understanding the complex function of chromatin remodeling and transcriptional regulation of specific gene expression in skeletal tissue.

Bone and Bones↗
PubMed2007

Dynamic histone acetylation/deacetylation with progesterone receptor-mediated transcription.

Histone acetylation is a highly dynamic posttranslational modification that plays an important role in gene expression. Previous work showed that promoter histone deacetylation is accompanied by progesterone receptor (PR)-mediated activation of the mouse mammary tumor virus (MMTV) promoter. We investigated the role of this deacetylation and found that this histone deacetylation is not a singular event. In fact, histone acetylation at the MMTV promoter is highly dynamic, with an initial increase in acetylation followed by an eventual net deacetylation of histone H4. The timing of increase in acetylation of H4 coincides with the time at which PR, RNA polymerase II, and histone acetyltransferases cAMP response element-binding protein (CREB)-binding protein and p300 are recruited to the MMTV promoter. The timing in which histone H4 deacetylation occurs (after PR and RNA polymerase II recruitment) and the limited effect that trichostatin A and small interfering RNA knockdown of histone deacetylase (HDAC)3 have on MMTV transcription suggests that this deacetylation activity is not required for the initiation of PR-mediated transcription. Interestingly, two HDACs, HDAC1 and HDAC3, are already present at the MMTV before transcription activation. HDAC association at the MMTV promoter fluctuates during the hormone treatment. In particular, HDAC3 is temporarily undetected at the MMTV promoter within minutes after hormone treatment when the histone H4 acetylation increases but returns to the promoter near the time when histone acetylation levels start to decline. These results demonstrate the dynamic nature of coactivator/corepressor-promoter association and histone modifications such as acetylation during a transcription activation event.

Acetylation↗
PubMed2001

Dynamic chromatin remodeling on the HER2 promoter in human breast cancer cells.

Deregulation of the HER2 oncogene occurs in 30% of human breast cancers and correlates with poor prognosis and increased propensity for metastasis. Since the molecular basis of HER2 overexpression in human cancers is not known, we sought to determine whether chromatin remodeling pathways are involved in the regulation of HER2 expression. We report that compared with breast cancer cells expressing a low level of HER2, HER2-overexpressing breast cancer cells contained significantly higher levels of acetylated and phosphorylated histone H3, and acetylated histone H4 associated with the HER2 promoter. Decreased recruitment of histone deacetylases in the promoter is also noted in the HER2-overexpressing cell. The association of acetylated histone H4 with HER2 gene chromatin and HER2 expression in breast cancer cells was upregulated by an inhibitor of histone deacetylases. Treatment with histone deacetylase inhibitor also reduced the association of histone deacetylase-1 and -2 with the HER2 promoter. In addition, the tumor promoters 12-O-tetradecanoylphorbol-13-acetate and okadaic acid stimulated the association of phosphorylated histone H3 on serine 10 with the HER2 promoter and also stimulated HER2 expression. These findings identify histone acetylation and histone phosphorylation as novel regulatory modifications that target HER2 gene chromatin, and suggest that elevated levels of these chromatin-relaxing components in the vicinity of the HER2 gene promoter may constitute an important non-genomic mechanism of HER2 overexpression in human breast cancer.

Acetylation↗
PubMed2000

Persistence of motor adaptation during constrained, multi-joint, arm movements.

We studied the stability of changes in motor performance associated with adaptation to a novel dynamic environment during goal-directed movements of the dominant arm. Eleven normal, human subjects made targeted reaching movements in the horizontal plane while holding the handle of a two-joint robotic manipulator. This robot was programmed to generate a novel viscous force field that perturbed the limb perpendicular to the desired direction of movement. Following adaptation to this force field, we sought to determine the relative role of kinematic errors and dynamic criteria in promoting recovery from the adapted state. In particular, we compared kinematic and dynamic measures of performance when kinematic errors were allowed to occur after removal of the viscous fields, or prevented by imposing a simulated, mechanical "channel" on movements. Hand forces recorded at the handle revealed that when kinematic errors were prevented from occurring by the application of the channel, recovery from adaptation to the novel field was much slower compared with when kinematic aftereffects were allowed to take place. In particular, when kinematic errors were prevented, subjects persisted in generating large forces that were unnecessary to generate an accurate reach. The magnitude of these forces decreased slowly over time, at a much slower rate than when subjects were allowed to make kinematic errors. This finding provides strong experimental evidence that both kinematic and dynamic criteria influence motor adaptation, and that kinematic-dependent factors play a dominant role in the rapid loss of adaptation after restoring the original dynamics.

Adaptation, Physiological↗