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Results for “Promoter dynamics”

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At least 253 records · Page 14Linked to original sources
PubMed2004

1,25-Dihydroxyvitamin D3 stimulates cyclic vitamin D receptor/retinoid X receptor DNA-binding, co-activator recruitment, and histone acetylation in intact osteoblasts.

UNLABELLED: 1,25(OH)2D3 induces gene expression through the VDR. We used chromatin immunoprecipitation techniques to explore this 1,25(OH)2D3-induced process on the 25-hydroxyvitamin D3-24-hydroxylase (Cyp24) and Opn gene promoters in intact osteoblasts. Our studies show that 1,25(OH)2D3-induced transactivation is a dynamic process that involves promoter-specific localization of VDR and RXR, recruitment of histone acetyltransferase complexes, and in the case of the Cyp24 gene, modification of histone 4. INTRODUCTION: The vitamin D receptor (VDR) binds as a retinoid X receptor (RXR) heterodimer to target DNA sequences and facilitates the recruitment of protein complexes that are essential for transcriptional modulation. These complexes include an acetyltransferase component that contains members of the p160 family and p300/CBP as well as human mediator that contains D receptor interacting protein (DRIP205). The objective of this study was to investigate the kinetics of VDR/RXR binding to 25-hydroxyvitamin D3-24-hydroxylase (Cyp24) and osteopontin (Opn) target gene promoters and to explore the recruitment and subsequent activities of co-activator complexes on these target genes in intact cells. MATERIALS AND METHODS: Mouse osteoblastic MC3T3-E1 cells and mouse primary calvarial osteoblasts (MOBs) were cultured in alphaMEM medium supplemented with 10% FBS. Confluent cells were treated with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or the vitamin D antagonist ZK159222, and the ability of these compounds to induce localization of VDR and RXR to specific regions of Cyp24 and Opn target genes was examined using chromatin immunoprecipitation techniques. The ability of both compounds to induce the recruitment of co-activator proteins such as p160 family members, CBP and DRIP205, and to increase the level of histone acetylation on the two gene promoters in MC3T3-E1 cells was also examined. RESULTS: 1,25(OH)2D3 induces rapid association of the VDR and RXR with both the Cyp24 and the Opn gene promoters in both MC3T3-E1 osteoblasts and MOBs, interactions that are both rapid and cyclic in nature. 1,25(OH)2D3 treatment also induces rapid recruitment of co-regulators such as SRC-1, -2, and -3, CBP, and p300 to both promoters, recruitment that leads to acetylation of histone 4 on Cyp24 but not the Opn. DRIP205 is also recruited to the two promoters in response to hormonal stimulation, an appearance that correlates directly with entry of RNA pol II. Studies with the vitamin D antagonist ZK159222 suggest a complex mode of action of this compound in blocking 1,25(OH)2D3-induced transcription. Our studies indicate that 1,25(OH)2D3-induced transactivation in intact osteoblasts is a dynamic process that involves promoter-specific localization of VDR and RXR as well as the recruitment of a number of co-regulators essential to 1,25(OH)2D3-induced transcription. CONCLUSIONS: We conclude that co-regulators essential for the transcriptional activity of the steroid receptor gene family are indeed critical for the actions of 1,25(OH)2D3. Selective use of co-regulators by target genes, however, may provide a mechanism for the unique and perhaps gene-selective responses observed with synthetic analogs such as ZK159222.

Acetylation↗
PubMed1997

Coactivation of human alpha1- and alpha2-globin genes in single induced MEL cells containing one human alpha-globin locus.

We developed a reverse-transcription polymerase chain reaction assay, performed on single isolated cells, to demonstrate the coexpression of human alpha1- and alpha2-globin mRNA in induced mouse erythroleukemic cells containing a single human alpha-globin locus. These results indicate that both alpha1 and alpha2 genes are activated from the same alpha-globin gene locus implying that HS-40-dependent transcriptional activation is mediated, either by a simultaneous interaction of HS-40 with both a alpha1 and alpha2-globin gene promoters, or by a dynamic process characterized by alternative, but short-lived, interactions with each alpha-globin gene promoter.

Animals↗
PubMed1982

Family theory and family therapy models: comparative review with implications for nursing practice.

Although theories of the family and theories of family therapy have different origins and purposes, both provide the basis for a family focused nursing approach. Family theory is a practice theory with a focus on health while family therapy is a practice theory with a focus on pathology. Thus, the contributions of each are different. For nurses to adapt and apply the principles of the two theories correctly, they first must understand whether application of a basic theory with a focus on health or a practice theory with a focus on pathology is appropriate in the particular nursing situation. For example, if a husband is hospitalized, recovering from a myocardial infarction, a family focused nursing approach is mandatory in providing optimal nursing care. Assessment of the family situation will provide clues for the functional or dysfunctional state of the family and the appropriateness of utilizing family theory or family therapy principles. If the current state of family relationships is optimal, application of family theory principles than can be applied to guide health promotion on a family level is appropriate. Organizational and dynamic aspects of the family promoting the husband's recovery can be accentuated, supported, and emphasized in the nursing care. However, if the current state of family relationships is pathological, application of family therapy principles is appropriate. Here the goal of the nursing care is restoration of functional organizational patterns and interactive processes between family members.

Family↗
PubMed2006

Dynamics of fresh and freeze-dried strawberry and red onion by quasielastic neutron scattering.

The microscopic behavior of fresh and freeze-dried strawberry and red onion at different water contents (45 and 20 wt % water) has been investigated by quasielastic neutron scattering (QENS). To distinguish between the dynamics of the water and the biological material isotopic (H/D) substitution was used. The results show that all samples exhibit an onset of anharmonic motions on the experimental time scale (3-100 ps) at about 230-240 K. Above 250 K the dynamics is mainly of translational character and strongly dependent on the hydration level. The diffusion constant increases rapidly with increasing water content and at 280 K it is approximately 20% higher for the hydration water in freeze-dried strawberry than in freeze-dried red onion and around 2 orders of magnitude faster for the hydration water than for the biological material. Moreover, the diffusion constant of the biological part is about 50% faster in freeze-dried strawberry than in freeze-dried red onion. It was also found that the average relaxation time is slightly faster in fresh strawberry than in freeze-dried strawberry. From the results we can conclude that the water dynamics is not only promoting motions in the biological material, it is also affected by the structure (and possibly also the dynamics) of the biological material. Thus, the microscopic properties of the biological materials are interrelated with the properties of their hydration water.

Fragaria↗
PubMed1994

Neutrophil derived cathepsin G induces potentially thrombogenic changes in human endothelial cells: a scanning electron microscopy study in static and dynamic conditions.

Activated neutrophils may promote thrombus formation by releasing proteases which may activate platelets, impair the fibrinolytic balance and injure the endothelial monolayer. We have investigated the morphological correlates of damage induced by activated neutrophils on the vascular wall, in particular the vascular injury induced by released cathepsin G in both static and dynamic conditions. Human umbilical vein endothelial cells were studied both in a cell culture system and in a model of perfused umbilical veins. At scanning electron microscopy, progressive alterations of the cell monolayer resulted in cell contraction, disruption of the intercellular contacts, formation of gaps and cell detachment. Contraction was associated with shape change of the endothelial cells, that appeared star-like, while the underlying extracellular matrix, a potentially thrombogenic surface, was exposed. Comparable cellular response was observed in an "in vivo" model of perfused rat arterial segment. Interestingly, cathepsin G was active at lower concentrations in perfused vessels than in culture systems. Restoration of blood flow in the arterial segment previously damaged by cathepsin G caused adhesion and spreading of platelets on the surface of the exposed extracellular matrix. The subsequent deposition of a fibrin network among adherent platelets, could be at least partially ascribed to the inhibition by cathepsin G of the vascular fibrinolytic potential. This study supports the suggestion that the release of cathepsin G by activated neutrophils, f.i. during inflammation, may contribute to thrombus formation by inducing extensive vascular damage.

Animals↗
PubMed2005

Role of nutrient bound of prey on the dynamics of predator-mediated competitive-coexistence.

The coexistence of competitive species with a shared predator is well established. The effect of 'food-value' on predator-prey dynamics has also received much attention. However, the study of a nutrient bound of prey, specifically on predator-mediated competitive-coexistence has not received much attention. Here we study the effects of the caloric content or a nutrient bound of prey on the dynamics of competitive-coexistence with the shared predator in a specific model. We propose and analyze a mathematical model for exploitative competition of two prey species with a shared predator. The change of dynamic stability due to the variation of a nutrient bound of each prey on predator-mediated dynamics is studied through extensive numerical experiments. Our analytical and numerical results demonstrate that variation in a nutrient bound promotes the switching of dynamics and may be treated as a driving force for the dynamics of competitive-coexistence with the shared predator.

Animal Nutritional Physiological Phenomena↗
PubMed1991

[Effectiveness of using external laser irradiation in the complex treatment of patients with pulmonary tuberculosis with concomitant bronchial obstruction syndrome].

External laser radiation (ELP) (18-20 daily procedures) was used together with chemotherapy in the combined treatment of 53 patients with destructive pulmonary tuberculosis characterized by delayed dynamics of the process and concurrent obstructive bronchial syndrome. ELR promoted acceleration of the process dynamics, closure of disintegration cavities and alleviation of bronchial obstruction phenomena. The mechanisms of a favourable ELR action were essentially due to the reduction of basal oxidative metabolism and enhancement of defensive reaction during contact with a specific pathogen in phagocytes, which was confirmed by the recorded results of the spontaneous and stimulated by the killed BCG culture NST rest in peripheral neutrophils and monocytes.

Adult↗
PubMed2004

Wnt-responsive element controls Lef-1 promoter expression during submucosal gland morphogenesis.

Regulated expression of lymphoid enhancer factor 1 (Lef-1) plays an obligatory role in the transcriptional control of epithelial bud formation during airway submucosal gland and mammary gland development. However, regions of the Lef-1 promoter required for spatial and temporal regulation during glandular development have yet to be defined. We hypothesized that a previously reported 110-bp Wnt-responsive element (WRE) in the Lef-1 promoter, which can be induced by Wnt-3a/beta-catenin signals, may also play a role in regulating Lef-1 expression during airway and mammary gland development. Here we show that the Lef-1 promoter is also responsive to Wnt-1 signals in both airway and mammary epithelial cell lines. To better understand the importance of the WRE in dynamically regulating Lef-1 promoter activation in these two types of epithelia in vivo, we utilized LacZ reporter transgenic mice to evaluate the significance of Wnt-responsive sequences in the Lef-1 promoter during glandular bud formation. A 2.5-kb Lef-1 promoter fragment partially reproduced endogenous Lef-1 expression patterns in a subset of cell types involved in both mammary gland and submucosal glandular bud development. Interestingly, removal of the 110-bp WRE from the Lef-1 promoter ablated expression in nasal and tracheal submucosal glandular buds while having no significant effect on developmental expression in mammary glandular buds. These findings suggest that Wnt regulation of the Lef-1 promoter at the WRE may play an important role during airway submucosal glandular bud formation.

Animals↗
PubMed2005

Tumor necrosis factor-alpha activates the human prolactin gene promoter via nuclear factor-kappaB signaling.

Pituitary function has been shown to be regulated by an increasing number of intrapituitary factors, including cytokines. Here we show that the important cytokine TNF-alpha activates prolactin gene transcription in pituitary GH3 cells stably expressing luciferase under control of 5 kb of the human prolactin promoter. Similar regulation of the endogenous rat prolactin gene by TNF-alpha in GH3 cells was confirmed using real-time PCR. Luminescence microscopy revealed heterogeneous dynamic response patterns of promoter activity in individual cells. In GH3 cells treated with TNF-alpha, Western blot analysis showed rapid inhibitory protein kappaB (IkappaBalpha) degradation and phosphorylation of p65. Confocal microscopy of cells expressing fluorescence-labeled p65 and IkappaBalpha fusion proteins showed transient cytoplasmic-nuclear translocation and subsequent oscillations in p65 localization and confirmed IkappaBalpha degradation. This was associated with increased nuclear factor kappaB (NF-kappaB)-mediated transcription from an NF-kappaB-responsive luciferase reporter construct. Disruption of NF-kappaB signaling by expression of dominant-negative variants of IkappaB kinases or truncated IkappaBalpha abolished TNF-alpha activation of the prolactin promoter, suggesting that this effect was mediated by NF-kappaB. TNF-alpha signaling was found to interact with other endocrine signals to regulate prolactin gene expression and is likely to be a major paracrine modulator of lactotroph function.

Animals↗
PubMed2025

Should I stay or should I go: TFIIIC as assembly factor and barrier in RNA polymerase III transcription.

Critical for the regulation of eukaryotic gene transcription is the assembly and interplay of general transcription factors (GTFs) with RNA polymerases (RNAPs), leading to the formation of pre-initiation complexes (PICs) as a rate-limiting step in transcription activation. Compared with RNAPII PIC assembly involving many GTFs, activators, and co-activators, RNAPIII PIC assembly is less complex, involving mainly the four GTFs TFIIIA, TFIIIB, TFIIIC, and snRNA activating protein complex with only a few additional factors. The RNAPIII-specific GTF TFIIIC is present in type I and II promoters. One prominent area of investigation has been the dynamic interaction between TFIIIC and its promoter elements, the varying affinities of TFIIIC toward these elements, and the flexible linker within TFIIIC. Additionally, evidence suggests that TFIIIC may play a dual role, acting as an assembly factor that positions TFIIIB during PIC formation and as a barrier during RNAPIII-mediated transcription. By summarizing recent structural, biochemical, and genomic data, this review explores the mechanisms by which RNAPIII-specific GTFs, with a focus on TFIIIC, dynamically regulate RNAPIII transcription.

RNA Polymerase III↗
PubMed2005

Role of protein dynamics in reaction rate enhancement by enzymes.

An integrated view of protein structure, dynamics, and function is emerging, where proteins are considered as dynamically active assemblies and internal motions are closely linked to function such as enzyme catalysis. Further, the motion of solvent bound to external regions of protein impacts internal motions and, therefore, protein function. Recently, we discovered a network of protein vibrations in enzyme cyclophilin A, coupled to its catalytic activity of peptidyl-prolyl cis-trans isomerization. Detailed studies suggest that this network, extending from surface regions to active site, is a conserved part of enzyme structure and has a role in promoting catalysis. In this report, theoretical investigations of concerted conformational fluctuations occurring on microsecond and longer time scales within the discovered network are presented. Using a new technique, kinetic energy was added to protein vibrational modes corresponding to conformational fluctuations in the network. The results reveal that protein dynamics promotes catalysis by altering transition state barrier crossing behavior of reaction trajectories. An increase in transmission coefficient and number of productive trajectories with increasing amounts of kinetic energy in vibrational modes is observed. Variations in active site enzyme-substrate interactions near transition state are found to be correlated with barrier recrossings. Simulations also showed that energy transferred from first solvation shell to surface residues impacts catalysis through network fluctuations. The detailed characterization of network presented here indicates that protein dynamics plays a role in rate enhancement by enzymes. Therefore, coupled networks in enzymes have wide implications in understanding allostericity and cooperative effects, as well as protein engineering and drug design.

Binding Sites↗
PubMed2005

Epigenetic control of MHC-II: interplay between CIITA and histone-modifying enzymes.

Recent advances have shown the crucial role of histone-modifying enzymes in controlling gene activation and repression. This led to the 'histone code' hypothesis, which proposes that combinations of histone modifications work in concert to affect specific gene expression. Mounting evidence suggests that the class II transactivator modulates promoter accessibility by coordinating the recruitment of chromatin modifiers in a time-dependent fashion. MHC-II expression is exquisitely controlled by these highly specific, coordinated and dynamic interactions at the promoter.

Animals↗
PubMed2002

Looking over the edge: a new role for Ena/VASP proteins in lamellipodial dynamics.

How can Ena/VASP proteins promote actin-based movement of the intracellular pathogen Listeria or rapid protrusion of lamellipodia but at the same time inhibit cell translocation? A report in the May 17(th) issue of Cell now offers a possible explanation for this conundrum. Bear et al. report that Ena/VASP proteins regulate cell motility by competing with capping proteins to control actin filament length and geometry at the leading edge of cells.

Actin Depolymerizing Factors↗
PubMed2000

Molecular dynamics simulations of bovine cathepsin B and its complex with CA074.

To promote our better understanding of the dynamic stability of the bovine cathepsin B structure, which is characterized by an extra disulfide bond at Cys148-Cys252 from the other species, and of the binding stability of CA074 (a cathepsin B-specific inhibitor), molecular dynamics (MD) simulations were performed for the enzyme and its CA074 complex, assuming a system in aqueous solution at 300 K. The MD simulation covering 400 ps indicated that the existence of a Cys148-Cys252 disulfide bond increases the conformational flexibility of the occluding loop, although the conformational stability of the overall structure is little affected. The structural characteristics of the complex elucidated by X-ray analysis were suggested to be also intrinsic and stable in the dynamic state; the hydrogen bonding/electrostatic interactions between the main and side chains of CA074 and the Sn and Sn' subsites of the enzyme were maintained throughout the MD simulation. Furthermore, the simulation made clear that the binding of CA074 significantly restricted the conformational flexibility of the substrate binding region, especially the occluding loop, of cathepsin B. Statistical analyses during the simulation suggest that the selectivity of CA074 for cathepsin B stems from the tight P1'-S1' and P2'-S2' interactions, assisted in particular by double hydrogen bonds between the carboxyl two oxygens of the CA074 C-terminus and the imidazole NH groups of His110 and His111 residues.

Animals↗
PubMed1990

New techniques for weaning difficult patients from mechanical ventilation.

This article compares the weaning of challenging patients from mechanical ventilation to an exercise training program experienced by many athletes. Physically, the importance of the correction and maintenance of chronic health issues, nutrition, and hydration are explored. Psychologically, the degree of preparedness by both the patient and the health care team is presented. Parameters for predicting readiness to wean that include both objective and subjective indices are gaining more support; two tools for weaning are offered. During the weaning process, reconditioning of the respiratory muscles can be promoted through endurance or strengthening exercises or a combination of both. The quality and quantity of exercise performed must be closely monitored to prevent respiratory muscle fatigue or atrophy. Newer modes of ventilation, including pressure support ventilation, mandatory minute ventilation, and continuous flow, decrease the work of breathing, promote ventilator/patient synchrony, and provide a more dynamic weaning process. All of these modes promote exercise, and augment the physical and psychological components of weaning. Nursing considerations for successful weaning are offered.

Adult↗
PubMed2005

Dynamic control of lymphocyte trafficking by fever-range thermal stress.

Migration of blood-borne lymphocytes into tissues involves a tightly orchestrated sequence of adhesion events. Adhesion molecules and chemokine receptors on the surface of circulating lymphocytes initiate contact with specialized endothelial cells under hemodynamic shear prior to extravasation across the vascular barrier into tissues. Lymphocyte-endothelial adhesion occurs preferentially in high endothelial venules (HEV) of peripheral lymphoid organs. The continuous recirculation of naïve and central memory lymphocytes across lymph node and Peyer's patch HEV underlies immune surveillance and immune homeostasis. Lymphocyte-endothelial interactions are markedly enhanced in HEV-like vessels of extralymphoid organs during physiological responses associated with acute and chronic inflammation. Similar adhesive mechanisms must be invoked for efficient trafficking of immune effector cells to tumor sites in order for the immune system to have an impact on tumor progression. Here we discuss recent evidence for the role of fever-range thermal stress in promoting lymphocyte-endothelial adhesion and trafficking across HEV in peripheral lymphoid organs. Findings are also presented that support the hypothesis that lymphocyte-endothelial interactions are limited within tumor microenvironments. Further understanding of the molecular mechanisms that dynamically promote lymphocyte trafficking in HEV may provide the basis for novel approaches to improve recruitment of immune effector cells to tumor sites.

Animals↗
PubMed2000

Developmentally dynamic histone acetylation pattern of a tissue-specific chromatin domain.

We have defined the histone acetylation pattern of the endogenous murine beta-globin domain, which contains the erythroidspecific beta-globin genes. The beta-globin locus control region (LCR) and transcriptionally active promoters were enriched in acetylated histones in fetal liver relative to fetal brain, whereas the inactive promoters were hypoacetylated. In contrast, the LCR and both active and inactive promoters were hyperacetylated in yolk sac. Hypersensitive site two of the LCR was also hyperacetylated in murine embryonic stem cells, whereas beta-globin promoters were hypoacetylated. Thus, the acetylation pattern varied at different developmental stages. Histone deacetylase inhibition selectively increased acetylation at a hypoacetylated promoter in fetal liver, suggesting that active deacetylation contributes to silencing of promoters. We propose that dynamic histone acetylation and deacetylation play an important role in the developmental control of beta-globin gene expression.

Acetylation↗
PubMed2006

Suppression of MIP-1beta transcription in human T cells is regulated by inducible cAMP early repressor (ICER).

Local production of macrophage inflammatory protein-1beta (MIP-1beta), a beta-chemokine that blocks human immunodeficiency virus type 1 (HIV-1) entry into CD4+ CC chemokine receptor 5+ target cells, may be a significant factor in resistance to HIV-1 infection and control of local viral spread. The mechanisms governing MIP-1beta expression in T cells, however, are not well understood. Our results suggest that MIP-1beta RNA expression in T cells is dynamically regulated by transcriptional factors of the cyclic adenosine monophosphate (cAMP) responsive element (CRE)-binding (CREB)/modulator family. Transient transfection of primary human T cells with 5' deletion and site-specific mutants of the human MIP-1beta promoter identified an activated protein-1 (AP-1)/CRE-like motif at position -74 to -65 base pairs, relative to the TATA box as a vital cis-acting element and a binding site for inducible cAMP early repressor (ICER). Ectopic expression of ICER or induction of endogenous ICER with the cAMP agonists forskolin and prostaglandin E2 resulted in the formation of ICER-containing complexes, including an ICER:CREB heterodimer to the AP-1/CRE-like site and inhibition of MIP-1beta promoter activity. Our data characterize an important binding site for the dominant-negative regulator ICER in the MIP-1beta promoter and suggest that dynamic changes in the relative levels of ICER and CREB play a crucial role in cAMP-mediated attenuation of MIP-1beta transcription in human T cells.

Base Sequence↗