SEARCH · PubMed Health

Results for “Genes, Immediate-Early”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources

PubMed2026

An acute dose of glyphosate alters novel object exploration and hippocampal cFos expression in a sex-dependent manner in wildtype mice.

Glyphosate (GLY) is the active ingredient in most herbicides, including off-the-shelf weed killers such as Roundup®. GLY crosses the blood-brain barrier, increases oxidative stress and genotoxicity, and impacts reproduction, but the extent of its effects remains unclear. Previous research reports conflicting evidence on sex-specific susceptibility to GLY's effects, and very few investigate the effects of a single, acute dose on learning, memory, and neuronal activation. In vitro studies have found GLY interferes with gene expression and is uniquely capable of inducing DNA double strand breaks (DSBs) compared to other herbicides. DSBs can induce expression of immediate early genes (IEGs), which are important for synaptic plasticity, learning, and memory. However, a clear connection between GLY, IEGs, and learning and memory has yet to be made. To explore this, we tested male and female wildtype mice in novel object recognition after they received an acute, oral dose of 0, 250, or 500 mg/kg of GLY and assessed hippocampal DSB and IEG levels. We hypothesized that a single dose of GLY would impair memory by disrupting IEG expression and would affect males more than females. We did not find robust evidence that GLY impaired memory, though females that received 500 mg/kg did not explore the novel object more than the familiar. Hippocampal DSBs were decreased following 500 mg/kg in both sexes, yet hippocampal IEG immunoreactivity was decreased in GLY-exposed males only, revealing a complex sex-dependent relationship. These data add to the literature that GLY is potentially detrimental, highlighting the need for further investigations.

Animals↗

PubMed2026

Biophysical mechanisms underlying the generation and maintenance of rule-learning engram.

Training rodents in a particularly difficult olfactory-discrimination task results with acquisition of high-skill to perform the task superbly, termed 'rule-learning'. We show that rule-learning occurs abruptly, in a "light-bulb moment". Using whole-cell patch-clamp recordings from the piriform cortex (PC) of Fos2A-iCreER/TRAP2 mice, we target activated-neurons, expressing immediate early genes (IEG). We notice, from the onset of training, IEG-positive neurons from trained animals display enhanced intrinsic excitability. Subsequently, synaptic excitation and inhibition are enhanced in these neurons, in a coordinated, cell-wide process. Additionally, in parallel, we detect the density of IEG-expressing neurons sharply declines. Double labeling with TRAP and c-Fos reveal that nearly two-thirds of the rule-memory cell ensemble neurons are activated from the beginning of training. Silencing TRAP-expressing neurons using inhibitory DREADD leads to a complete loss of rule memory. Hence, we propose that rule learning occurs at a discrete moment and is developed through a gradual process that stabilizes the memory of the rule.

Animals↗

PubMed2026

Male and Female Mice Show Similar Fear Memory Performance Despite Hippocampal Immediate Early Gene Expression Differences During Encoding and Consolidation.

Accurate and efficient memory processing is essential for survival. A body of ongoing work in both human subjects and animal models suggests that memory processing may differ substantially between males and females. In mice, contextual fear memory (CFM) encoding, consolidation, and recall have been well studied, and the mouse hippocampus and amygdala have been implicated in these processes. The present pilot study addresses whether the activation of these brain regions differs substantially between male and female mice at each stage of CFM processing. We find that male and female mice show no differences in sleep behavior, which is essential for CFM consolidation, following single-trial contextual fear conditioning (CFC). We also find no significant differences in CFM recall performance between male and female mice. However, females show a trend for larger increases in CA1 cFos expression, relative to males, during CFM encoding. On the other hand, only males-but not females-show an apparent increase in cFos expression among dentate gyrus (DG) granule cells during CFM consolidation. Males also show a trend for a larger apparent reduction in cFos in CA1 and CA3 during CFM consolidation, relative to females. These preliminary findings highlight the idea that the neurobiological underpinnings of memory processing may differ between males and females, even when performance during recall is identical.

Animals↗

PubMed1992

Analysis of immediate-early transcripts of equine cytomegalovirus.

Equine cytomegalovirus (ECMV) contains a linear, double-stranded DNA genome composed of a 146-kbp unique region flanked by a pair of 18-kbp direct repeat (DR) sequences at the termini. Cycloheximide, actinomycin D, and phosphonoacetic acid were applied to infected cell cultures to divide viral transcription into immediate-early (IE), early, and late phases. Eight IE transcripts were identified and mapped to two regions (I and II) of the viral genome. Two of these IE RNAs (13.0 and 5.5 kb in size) were transcribed from region I, which is located within the DR regions; these IE genes are diploid. The other IE transcripts (17.0, 9.0, 7.2, 6.8, 4.5, and 4.2 kb) originated from region II. IE region II is adjacent to region I and spans both unique and DR sequences at the left terminus of the genome. Region II IE transcripts are spliced and transcribed in the opposite direction from region I IE transcripts. IE transcripts from region I were present throughout the replication cycle, whereas those from region II were more abundant during the IE stage than at the early and late stages of infection. These studies demonstrate that ECMV differs from other herpesviruses in the organization and unusually large transcription units of its IE genes.

Antigens, Viral↗

PubMed1992

Evidence that the herpes simplex virus immediate early protein ICP27 acts post-transcriptionally during infection to regulate gene expression.

The herpes simplex virus (HSV-1) immediate early protein ICP27 is a regulatory protein which is essential for virus replication. The phenotype of temperature-sensitive and deletion mutants in ICP27 includes overexpression of some immediate early and early gene products and greatly reduced levels of late gene products. To determine whether regulation by ICP27 occurs primarily at the transcriptional level, we have studied the expression of two immediate early products (ICP4 and ICP27) and two late gene products (glycoprotein B and glycoprotein C) at the level of transcription initiation, accumulation of steady state mRNA, and protein synthesis in an ICP27 temperature-sensitive mutant tsLG4, compared to wild-type HSV-1. At the nonpermissive temperature in tsLG4-infected cells, the two immediate early gene products ICP4 and ICP27 were overexpressed both at the mRNA and protein level although synthesis of these transcripts as measured by nuclear runoff assays was reduced relative to the wild-type HSV-1 infections. The transcription of late gene products glycoprotein B (gB) and glycoprotein C (gC) was lower in runoff assays from tsLG4 infections suggesting that the reduction in the level of late products occurred at the transcriptional level. However, temperature shift experiments in which tsLG4-infected cells were shifted to the nonpermissive temperature at various times after infection showed that the synthesis of late transcripts was not altered 2 hr after the shift whereas both the accumulation of leaky late and late mRNA and the incorporation of [35S]methionine into newly synthesized gB and gC was reduced by 2 hr after the shift to nonpermissive temperature. Therefore, while the synthesis of new transcripts continued, the accumulation of late mRNAs and their translation into protein was reduced when ICP27 was defective, whereas, the converse was found for immediate early products. That is, the synthesis of new transcripts was reduced yet mRNA and protein accumulated to high levels. These results suggest that ICP27 acts at least in part post-transcriptionally to regulate the expression of immediate early and late gene products.

Animals↗

PubMed1992

Reciprocal expression of c-jun, proline-rich protein and amylase genes during rat parotid salivary gland development.

We have investigated the temporal expression and cellular localization of the c-jun proto-oncogene and two major rat parotid gland secretory protein genes, PRP (proline-rich protein) and amylase, during postnatal development. c-jun mRNA steady-state levels increased at days 1, 7 and 14 after birth and decreased to basal levels at 21 days and older. PRP mRNA was first detected at 14 days and abruptly increased to adult levels at day 21. Amylase transcripts were first seen at day 7 and progressively increased to adult levels by 28 days. In situ hybridization demonstrated c-jun mRNA accumulation in the differentiating acinar cells and the ducts. The c-jun mRNA accumulation with time corresponds with the proliferative activity reported to occur in these two cellular populations. PRP transcripts were present exclusively in the well differentiated acinar cells while the accumulation of amylase mRNA corresponded to the progressive commitment of parotid cells to acinar differentiation. Our data suggest that during the postnatal development of the rat parotid gland: (a) c-jun expression associates with parotid gland proliferation and precedes the expression of PRP and amylase genes, and (b) activation of PRP and amylase genes is not concomitant and apparently occurs only in differentiating acinar cells.

Age Factors↗

PubMed1992

Proviral rearrangements and overexpression of a new cellular gene (nov) in myeloblastosis-associated virus type 1-induced nephroblastomas.

Histological and anatomopathological studies performed on 152 independent myeloblastosis-associated virus type 1 (MAV1)-induced nephroblastomas allowed us to precisely define the chronology of tumor development in chickens. Three tumors representing increasing developmental stages were used to construct genomic libraries and to study both the state of proviral genomes and the sites of MAV1 integration in genomic DNA. We established that increasing levels of proviral rearrangement, eventually leading to the elimination of infectious MAV genomes, were associated with tumor progression and that 22 individual tumors, representative of different developmental stages, did not contain any common MAV1 integration site. Cloning of cellular fragments flanking the MAV1-related proviruses in tumor DNA showed that each one of eight nephroblastomas tested expressed a high level of an as yet unidentified cellular gene (nov) whose transcription is normally arrested in adult kidney cells. Cloning of the normal nov gene established that in one tumor, fused long terminal repeat-truncated nov mRNA species were expressed, indicating that at least in that case, the high level of nov expression was under the control of the MAV long terminal repeat promoter. The normal nov gene encodes a putative 32-kDa secreted polypeptide, which is a member of a new family of proteins likely to be involved in cell growth regulation. We also showed that the expression of an amino-terminal-truncated nov product in chicken embryo fibroblasts was sufficient to induce their transformation.

Amino Acid Sequence↗

PubMed2026

A stable and potent buffalo EF1α1 promoter for robust gene expression in mammalian systems.

This study reports the first isolation and characterization of the buffalo EF1α1 promoter, demonstrating its strong gene expression activity both in vitro across diverse cultured cell types and in vivo across multiple mouse organs. Although viral promoters, such as cytomegalovirus (CMV) and simian virus (SV40), are widely used for their strong expression in various cell lines in mammalian expression systems and in animal tissues, they are prone to methylation-induced transcriptional silencing and subsequent loss of exogenous gene expression. The most effective alternative to viral promoters is the synthetic hybrid CAG promoter (cytomegalovirus major immediate-early enhancer combined with the chicken beta-actin promoter) or mammalian cellular promoter such as human elongation factor 1 alpha (hEF1α), which drives strong gene expression but lacks consistency and is limited in their in vivo expression potential due to their vulnerability to epigenetic silencing. To overcome these challenges, the bbEF1α1 promoter was cloned and evaluated both in vitro and in vivo. It consistently drives higher levels of exogenous gene expression than CMV in diverse cell lines. Importantly, transgene expression was achieved in various organs of transgenic mice and in muscle tissue following in vivo electroporation. These findings establish the bbEF1α1 promoter as a powerful ubiquitous driver of gene expression, offering high stability with broad applications in gene therapy, biopharmaceutical production, and functional genomics.

Animals↗

PubMed1978

Physical mapping of herpes simplex virus-coded functions and polypeptides by marker rescue and analysis of HSV-1/HSV-2 intertypic recombinants.

A number of temperature-sensitive (ts) mutants and one pyrimidine deoxyribonucleoside kinase-deficient mutant of herpes simplex virus (HSV), have been located on the physical map of the genome by means of marker rescue experiments and by the analysis of the crossover points in intertypic recombinants between HSV types 1 and 2. The physical map is compared to the genetic map and certain anomalies identified. Analysis of infected-cell polypeptides specified by intertypic recombinants has allowed tentative map co-ordinates to be assigned to the structural genes (or genes which cause post-translational modification) for many of the polypeptides. Immediate-early, phosphorylated, glycosylated and structural as well as non-structural polypeptides have been analysed in this way and it can be concluded that there is no restriction of any of these groups of polypeptides to either the long or the short regions of the genome. One of the recombinants, 2853, is at least partially "frozen" in one orientation of the long region. This orientation is also the one which exhibits a minimum number of crossovers in three other recombinants.

Chromosome Mapping↗

PubMed1992

The ICP4 binding sites in the herpes simplex virus type 1 glycoprotein D (gD) promoter are not essential for efficient gD transcription during virus infection.

Activation of the early and late genes of herpes simplex virus type 1 during infection in tissue culture requires functional immediate-early regulatory protein ICP4. ICP4 is a specific DNA-binding protein which recognizes a variety of DNA sequences, many of which contain the consensus ATCGTC. In general, mutations which impair the ability of ICP4 to bind to DNA also eliminate its ability to activate viral early and late promoters both in transfection assays and in the infected cell. However, the role of ICP4 binding sites in the viral genome is unclear; many early and late promoters do not contain consensus binding sites in their vicinity. The glycoprotein D (gD) gene contains two well-characterized ICP4 binding sites upstream of its promoter and a third downstream of the transcription start site. Multimerization of one of these sites has been shown to increase the response of the gD promoter to ICP4 in transfection assays, while their removal reduces stimulation of the gD promoter by ICP4 in vitro. To assess the role of these binding sites during virus infection, we have constructed a recombinant viral genome which has mutations affecting all three. Comparison of the amounts of gD RNA synthesized by the recombinant and wild-type viruses indicated that the mutations had little or no effect on the activity of the gD promoter. Therefore, either the sites have no essential role in gD promoter regulation in the presence of all of the herpes simplex virus type 1 IE polypeptides during a normal infection or they can be functionally substituted by other ICP4 binding sites elsewhere in the genome.

Animals↗

PubMed1992

Characterization of an R-binding site mediating the R-induced activation of the Epstein-Barr virus BMLF1 promoter.

In cells latently infected with Epstein-Barr virus, the switch from latency to productive infection is linked to the expression of two Epstein-Barr virus transcription factors called EB1 and R. R is an enhancer factor, and an R-responsive element (RRE) has been identified in the BMLF1 promoter. In this study, we have used bidirectional deletion mutagenesis to delineate the BMLF1 RRE (RRE-M) to a 44-bp sequence. We also show that R expressed from a recombinant vaccinia virus protects RRE-M against digestion by DNase I. Using mobility shift assays and dimethyl sulfate interferences, we have characterized the contact points between in vitro-translated R and the DNA. R binds in vitro to one site by simultaneously contacting two sequences within the site, which are separated by 8 bp: 5'-catGTCCCtctatcatGGCGCagac-3'. Site-directed mutagenesis of this sequence completely impaired the binding of R in vitro and rendered the BMLF1 promoter nonresponsive to R. The results suggest that the R-inducible BMLF1 enhancer is composed of a single R-binding site, called RRE-M.

Binding Sites↗

PubMed2026

Repurposing anti-phage defenses to differentially arrest the viral lifecycle reveals the regulatory logic of a parasitic satellite.

Mobile genetic elements frequently encode defense mechanisms to protect their bacterial hosts from viral attack. In Vibrio cholerae, these defensive elements include phage-inducible chromosomal island-like elements (PLEs), which are phage satellites that act as highly specialized parasites of the lytic phage ICP1. While PLE transcriptional activation upon ICP1 infection is known to be temporally regulated, the underlying regulatory logic and dependencies on the progression of the phage's developmental program required for activation remain unclear. In this study, we took a novel approach to define these dependencies by introducing independent anti-phage defense systems, BREX and DarTG, as molecular roadblocks to impede the ICP1 lifecycle. We discovered that, for both ICP1 and PLE, late-stage gene expression is fundamentally uncoupled from genome replication, representing a striking departure from the standard paradigm for double-stranded DNA phages. While BREX restricts ICP1 to an immediate-early transcriptional state that stalls PLE activation, DarTG allows the phage to execute its full transcriptional cascade despite the total block in DNA replication. This permissive environment provides the necessary cue(s) for complete PLE induction, revealing that robust PLE activation is profoundly dependent on the transcriptional progression of its helper phage.IMPORTANCEBacteria and their viruses (phages) are locked in perpetual evolutionary conflict. Some bacteria harbor phage satellites, specialized parasites that are activated to hijack the phage's components to spread all the while inhibiting viral production. While some satellites respond to a single viral trigger, the regulation of many satellites, including clinically relevant phage-inducible chromosomal island-like elements (PLEs) in Vibrio cholerae, remains poorly understood. Here, we used bacterial defense systems as molecular roadblocks to probe how PLE activation depends on its helper phage. We found that severe disruptions to viral transcription stall PLE activation. Unexpectedly, both the virus and the satellite can execute their full transcriptional programs even when DNA replication is completely blocked, challenging a fundamental paradigm in virology. These insights reveal a sophisticated level of phage-satellite coordination, illustrating how satellite activation is tightly linked to the transcriptional state of its helper phage, a dependency that ultimately drives the dissemination of mobile genetic elements.

Vibrio cholerae↗

PubMed2026

Repurposing anti-phage defenses to differentially arrest the viral lifecycle reveals the regulatory logic of a parasitic satellite.

Journal Article↗

PubMed2025

Heat shock factor 2 regulates oncogenic gamma-herpesvirus gene expression by remodeling the chromatin at the ORF50 and BZLF1 promoter.

The Human gamma-herpesviruses Kaposi's sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV) are causally associated to a wide range of cancers. While the default infection program for these viruses is latent, sporadic lytic reactivation supports virus dissemination and oncogenesis. Despite its relevance, the repertoire of host factors governing the transition from latent to lytic phase is not yet complete, leaving much of this complex process unresolved. Here we show that heat shock factor 2 (HSF2), a transcription factor involved in regulation of stress responses and specific cell differentiation processes, promotes gamma-herpesvirus lytic gene expression. In lymphatic endothelial cells infected with KSHV and in gastric cancer cells positive for EBV, ectopic HSF2 enhances the expression of lytic genes; While knocking down HSF2 significantly decreases their expression. HSF2 overexpression is accompanied by decreased levels of repressive histone marks at the promoters of the lytic regulators KSHV ORF50 and EBV BZLF1, both characterized by poised chromatin features. Our results demonstrate that endogenous HSF2 binds to the promoters of KSHV ORF50 and EBV BZLF1 genes and shifts the bivalent chromatin state towards a more transcriptionally permissive state. We detected HSF2 binding to the ORF50 promoter in latent cells, in contrast, in lytic cells, HSF2 occupancy at the ORF50 promoter is lost in conjunction with its proteasomal degradation. These findings identify HSF2 as a regulator of gamma-herpesvirus lytic gene expression in latency and offer new insights on the function of this transcription factors at poised gene promoters, improving our understanding of its role in differentiation and development.

Humans↗

PubMed1992

Second-site homologous recombination in Epstein-Barr virus: insertion of type 1 EBNA 3 genes in place of type 2 has no effect on in vitro infection.

This study was undertaken to develop a general strategy for the introduction of mutations into specific sites in the Epstein-Barr virus (EBV) genome. Previous approaches were limited by the need for physical linkage of the transfected EBV DNA fragment to a positive selection marker. In our experiments, a positive selection marker was introduced into one site in the EBV genome and a distant, nonlinked, marker was introduced into another site. Each marker was on a large EBV DNA fragment and was inserted into the genome by transfection into cells carrying a resident EBV genome. The resident EBV genome was simultaneously induced to replicate by using a cotransfected expression plasmid for the EBV immediate-early transactivator, Z (J. Countryman, H. Jenson, R. Seibl, H. Wolf, and G. Miller, J. Virol. 61:3672-3679, 1987; G. Miller, M. Rabson, and L. Heston, J. Virol. 50:174-182, 1984). Eleven percent of the resultant EBV genomes which incorporated the positive selection marker also incorporated the nonlinked marker. Both markers uniformly targeted the homologous EBV genome site. In this way novel EBV recombinants were constructed in which the EBV type 1 EBNA 3A, EBV type 1 EBNA 3A and 3B, or EBV type 1 EBNA 3A, 3B, and 3C genes were introduced into a largely type 2 EBV genome, replacing the corresponding type 2 gene(s). No difference was observed in primary B-lymphocyte growth transformation, in latent EBV gene expression, or in spontaneous lytic EBV gene expression. These new recombinants should be useful for ongoing analyses of the type specificity of the immune response.

Amino Acid Sequence↗

PubMed1978

Physical mapping of herpes simplex virus-induced polypeptides.

Analysis of the polypeptides induced by 29 herpes simplex virus type 1/type 2 intertypic recombinants and correlation of the data with the crossover points in the recombinant DNAs have enabled the map positions of many polypeptides to be deduced. These include 25 polypeptides which label with [35S]methionine, 11 which label with [32P]orthophosphate, and 4 which label with [14C]glucosamine. Together with the data of Preston et al. (J. Virol., in press) on the mapping of five immediate-early polypeptides, the results show that representatives of four groups of proteins--immediate-early, late, phosphorylated, and glycosylated--map in both long and short regions. The functional organization of the herpes simplex virus genome does not therefore restrict any of these four groups to either the long or the short region.

Cell Line↗

PubMed2025

Transcriptional profiling of Hutchinson-Gilford Progeria patients identifies primary target pathways of progerin.

Hutchinson Gilford Progeria Syndrome (HGPS) is an ultra-rare pediatric premature aging disorder. The disease is caused by a point mutation in the LMNA gene leading to the production of the dominant-negative progerin isoform of the nuclear envelope protein lamin A. Disease severity and progression amongst the population of ~140 known patients is variable. Most of the mechanistic insights into the disease have come from studies using cellular or mouse models of HGPS. To probe the clinical relevance of previously implicated cellular pathways and to address the extent of gene expression heterogeneity between patients, we have performed transcriptomic analysis of a comprehensive set of HGPS patients. We find misexpression of several cellular pathways across the patient population, particularly of multiple signaling pathways as well as the Unfolded Protein Response (UPR) and mesodermal cell fate specification. Variability amongst individual patients was limited, with misregulation of the major pathways observed in most patients. Comparing the transcriptome of patients with an inducible HGPS cell model, we distinguished immediate-early cellular response pathways from secondary adaptive pathways and identified mTORC1, the UPR, UV response, apoptosis and TNFα signaling via NF-κB as primary targets of the disease-causing progerin protein.

Hutchinson-Gilford Progeria Syndrome↗

PubMed2024

Deciphering the molecular nexus of BTG2 in periodontitis and diabetic kidney disease.

OBJECTIVE: To investigate the role of BTG2 in periodontitis and diabetic kidney disease (DKD) and its potential underlying mechanism. METHODS: Gene expression data for periodontitis and DKD were acquired from the Gene Expression Omnibus (GEO) database. Differential expression analysis identified co-expressed genes between these conditions. The Nephroseq V5 online nephropathy database validated the role of these genes in DKD. Pearson correlation analysis identified genes associated with our target gene. We employed Gene Set Enrichment Analysis (GSEA) and Protein-Protein Interaction (PPI) networks to elucidate potential mechanisms. Expression levels of BTG2 mRNA were examined using quantitative polymerase Chain Reaction (qPCR) and immunofluorescence assays. Western blotting quantified proteins involved in epithelial-to-mesenchymal transition (EMT), apoptosis, mTORC1 signaling, and autophagy. Additionally, wound healing and flow cytometric apoptosis assays evaluated podocyte migration and apoptosis, respectively. RESULTS: Analysis of GEO database data revealed BTG2 as a commonly differentially expressed gene in both DKD and periodontitis. BTG2 expression was reduced in DKD compared to normal conditions and correlated with proteinuria. GSEA indicated enrichment of BTG2 in the EMT and mTORC1 signaling pathways. The PPI network highlighted BTG2's relevance to S100A9, S100A12, and FPR1. Immunofluorescence assays demonstrated significantly lower BTG2 expression in podocytes under high glucose (HG) conditions. Reduced BTG2 expression in HG-treated podocytes led to increased levels of EMT markers (α-SMA, vimentin) and the apoptotic protein Bim, alongside a decrease in nephrin. Lower BTG2 levels were associated with increased podocyte mobility and apoptosis, as well as elevated RPS6KB1 and mTOR levels, but reduced autophagy marker LC3. CONCLUSION: Our findings suggest that BTG2 is a crucial intermediary gene linking DKD and periodontitis. Modulating autophagy via inhibition of the mTORC1 signaling pathway, and consequently suppressing EMT, may be pivotal in the interplay between periodontitis and DKD.

Periodontitis↗