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At least 19 recordsLinked to original sources
PubMed1999

Involvement of serotonergic pathways in mediating the neuronal activity and genetic transcription of neuroendocrine corticotropin-releasing factor in the brain of systemically endotoxin-challenged rats.

The present study investigated the effect of serotonin depletion on the neuronal activity and transcription of corticotropin-releasing factor in the rat brain during the acute-phase response. Conscious male rats received an intraperitoneal (i.p.) injection with the immune activator lipopolysaccaride (25 microg/100 g body wt) after being treated for three consecutive days with para-chlorophenylalanine (30mg/100 g/day). This irreversible inhibitor of tryptophane-5-hydroxylase decreased hypothalamic serotonin levels by 96%. One, 3 and 6 h after a single i.p. injection of lipopolysaccharide or vehicle solution, rats were killed and their brains cut in 30-microm coronal sections. Messenger RNAs encoding c-fos, nerve-growth factor inducible-B gene, corticotropin-releasing factor and the heteronuclear RNA encoding corticotropin-releasing factor primary transcript were assayed by in situ hybridization using 35S-labeled riboprobes, whereas Fos-immunoreactive nuclei were labeled by immunocytochemistry. Lipopolysaccharide induced a wide neuronal activation indicated by the expression of both immediate-early gene transcripts and Fos protein in numerous structures of the brain. The signal for both immediate-early gene transcripts was low to moderate 1 h after lipopolysaccharide administration, maximal at 3 h and decline at 6 h post-injection, whereas at that time, Fos-immunoreactive nuclei were still detected in most of the c-fos messenger RNA-positive structures. Interestingly, the strong and widespread induction of both immediate-early gene transcripts was almost totally inhibited by para-chlorophenylalanine treatment; in the hypothalamic paraventricular nucleus for example, c-fos messenger RNA signal and the number of Fos-immunoreactive positive cells were reduced by 80 and 48%, respectively, in serotonin-depleted rats treated with the bacterial endotoxin. This blunted neuronal response was also associated with an attenuated stimulation of neuroendocrine corticotropin-releasing factor transcription and plasma corticosterone release. Indeed, lipopolysaccharide caused a selective expression of corticotropin-releasing factor primary transcript in the paraventricular nucleus of the hypothalamus and this effect was significantly reduced by treatment with the serotonin inhibitor. However, basal expression of corticotropin-releasing factor messenger RNA across the brain (bed nucleus of the stria terminalis, medial preoptic area, paraventricular nucleus of the hypothalamus, central nucleus of the amygdala, etc.) was not affected by the para-chlorophenylalanine treatment. These results suggest that the integrity of serotonin pathways plays a role in the neuronal activity triggered by the systemic endotoxin insult. The fact that serotonin depletion largely prevented activation of neurosecretory parvocellular neurons of the paraventricular nucleus of the hypothalamus and neuroendocrine corticotropin-releasing factor gene transcription in response to immunogenic challenge provides the evidence that serotonergic system is part of the brain circuitry involved in the corticotroph axis-immune interface.

Amygdala↗
PubMed1972

Selective inhibition of genetic transcription in sea urchin embryos. Incorporation of 5-bromodeoxyuridine into low molecular weight nuclear DNA.

Experimental evidence suggests that exposure of sea urchin gastrulae to 5-bromodeoxyuridine (BUdR), an analog of thymidine, causes a reduction in the rate of synthesis of some RNA species usually transcribed at this stage of development. In pulse-chase experiments, (3)H (in gastrula stage 8-15S nuclear DNA labeled with BUdR-(3)H) could not be chased, with unlabeled BUdR, into 20-60S size-range DNA; in similar experiments in which gastrulae were pulsed with thymidine-(3)H and then chased with unlabeled thymidine, (3)H in 8-15S nuclear DNA could be extensively chased into 20-60S DNA. DNA-RNA hybridization assays indicate that gastrula stage nuclear DNA in the range of 20-60S has greater sequence homology for gastrula stage RNA-(3)H than does nuclear DNA of similar size-range taken from gastrulae exposed to BUdR for 1 hr. An explanation is offered for the effect of BUdR on transcription and DNA replication in sea urchin embryos.

Animals↗
PubMed1964

IONIZING RADIATION: EFFECT ON GENETIC TRANSCRIPTION.

Cells of Escherichia coli grown on maltose can be induced by the addition of thiomethyl galactoside to produce beta-galactosidase. If cells are irradiated shortly after induction, the transcription of the DNA ceases, and the enzyme produced by the messenger RNA is observed to reach a maximum. From these data the calculated half-life of unstable messenger RNA is given over a temperature range from 8.1 minutes at 10 degrees C to 0.7 minute at 45 degrees C. The kinetics of cessation of transcription give information on both meassenger RNA decay and rate of transcription. Arrhenius graphs for both these rates are given, and the activation energies mtieasured are 11,000 calories per mole for decay and 22,000 calories per mole for transcription. This relation to temperature is characteristic of enzymatic behavior.

DNA↗
PubMed1976

Structural organization and processing of the genetic transcript in the cellular slime mold Dictyostelium discoideum.

The organization of the genome and the synthesis and processing of heterogeneous nuclear RNA (HNRNA) in the cellular slime mold Dictysotelium discoideum have been analyzed. Approximately 60-70% of the genome of Dictyostelium consists of interspersed reiterated and single-copy sequences. The interspersed reiterated sequences have an average length of 250-400 nucleotides. Approximately 50% of the reiterated DNA sequences consist of long noninterspersed sequences. The results of analyses of ynRNA synthesis and processing have been incorporated into a model. According to the model the primary genetic transcript of Dictyostelium is synthesized as a molecule that is 25% larger than mRNA. The bulk of the hnRNA is synthesized from a unit consisting of a short reiterated DNA sequence transcript at the 5' end of the molecule and a single-copy sequence of approximately 1,200 nucleotides in length. In the processing of the mRNA precursor, there appears to be a loss of the majority of the repetitive sequence at the 5' end. The genome contains interspersed sequences of poly (dT)25. These sequences, which appear to be at the 3' terminus of the transcription unit, are transcribed directly into the heterogenous nuclear RNA and are contained within the messenger RNA. During the processing of the heterogeneous nuclear RNA, a poly (A) sequence of approximately 125 nucleotides in length is added posttranscriptionally to the 3' end of the molecule.

Base Sequence↗
PubMedDate not supplied

[Genetic transcription in eukaryotes: from transcriptional factors to disease].

The organisms' genetic information is stored as DNA sequences: the genes. The most important level of gene expression regulation is exerted at the transfer process of this information from the genes into messenger RNA molecules; this process is called transcription and is carried out by a molecular machinery conformed by hundreds of different proteins which are assembled in an ordered step way. These proteins or transcriptional factors are classified according to their mode of action in 4 groups: general transcriptional factors, activators, coactivators and repressors. There are diseases like. Aniridia, the Rubinstein-Taybi syndrome and Hodgkin's disease, in which some transcriptional factor have been involved and in some, the molecular cause i.e. the mutations responsible for the molecular dysfunction in a transcriptional factor has been elucidated. Understanding at the molecular level the transcription process will help to comprehend the relationship of it with the development and health of the organism.

Eukaryotic Cells↗
PubMed1992

Individual stage selector element mutations lead to reciprocal changes in beta- vs. epsilon-globin gene transcription: genetic confirmation of promoter competition during globin gene switching.

Biochemical and genetic analysis of the embryonic to adult beta-like globin gene switch in chickens has led to the hypothesis that competition between the promoters of the cis-linked epsilon- and beta-globin genes for interaction with a shared enhancer mediates the developmental changes in expression of beta-globin protein isotypes. To test specific predictions of this promoter competition model, a sensitive RNA/polymerase chain reaction assay has been used to investigate the effects of individual beta-globin promoter mutations on expression of the two linked genes in transiently transfected erythroid cells. Mutations that attenuated adult beta-globin transcription resulted concomitantly in a proportional increase in expression of the embryonic epsilon-globin gene. Consistent with the model, mutations disrupting the binding sites for either of two adult stage-specific transcription factors (NF-E4 and beta CTF) indicate that these sites are essential both for induction of beta-globin gene expression and for indirect suppression (through promoter competition) of epsilon-globin transcription in definitive (adult) erythroid cells. These results provide direct evidence that stage-specific transcription factors affect the equilibrium existing between multiple interacting globin cis-regulatory elements. We conclude that promoter competition is an important mechanism through which developmental regulation of chicken beta-globin gene switching is achieved and that such competitive interactions may prove to be generally applicable to the regulation of a variety of other temporally or spatially restricted gene expression patterns.

Animals↗