Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “effector genes”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 91 records · Page 5Linked to original sources
PubMed2006

Interferons alpha and lambda inhibit hepatitis C virus replication with distinct signal transduction and gene regulation kinetics.

BACKGROUND & AIMS: Hepatitis C virus (HCV) is a major cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. Current therapy with pegylated interferon alpha (IFN-alpha) in combination with ribavirin is associated with adverse effects and often fails to induce a sustained response. IFN-lambdas, recently discovered IFN gene family members, exhibit antiviral and cell stimulatory activities similar to IFN-alpha. We aimed to determine whether IFN-lambda exhibits antiviral activity toward HCV and to compare the signal transduction and effector gene pathways with those of IFN-alpha. METHODS: Using the HCV replicon system and cell culture infectious reporter virus, we compared IFN-alpha and IFN-lambda effects on HCV RNA replication and protein expression, as measured by quantitative reverse-transcriptase polymerase chain reaction, luciferase expression, and Western blot. Receptor expression and signaling pathways were explored using flow cytometry and Western blot. IFN-alpha- and IFN-lambda-mediated gene expression changes were compared using microarray analyses. RESULTS: IFN-lambda exhibited dose- and time-dependent HCV inhibition, independent of types I and II IFN receptors. The kinetics of IFN-lambda-mediated signal transducers and activators of transcription (STAT) activation and induction of potential effector genes were distinct from those of IFN-alpha. IFN-lambda induced steady increases in levels of known interferon stimulated genes (ISGs), whereas IFN-alpha ISGs peaked early and declined rapidly. IFN-lambda inhibited replication of HCV genotypes 1 and 2 and enhanced the antiviral efficacy of subsaturating levels of IFN-alpha. CONCLUSIONS: These results demonstrate distinct differences in IFN-lambda- and IFN-alpha-induced antiviral states. Understanding these differences may prove useful for developing new HCV treatment strategies.

Antiviral Agents↗
PubMed2006

A Pseudomonas syringae pv. tomato avrE1/hopM1 mutant is severely reduced in growth and lesion formation in tomato.

The model plant pathogen Pseudomonas syringae pv. tomato DC3000 grows and produces necrotic lesions in the leaves of its host, tomato. Both abilities are dependent upon the hypersensitive response and pathogenicity (Hrp) type III secretion system (TTSS), which translocates multiple effector proteins into plant cells. A previously constructed DC3000 mutant with a 9.3-kb deletion in the Hrp pathogenicity island conserved effector locus (CEL) was strongly reduced in growth and lesion formation in tomato leaves. The ACEL mutation affects three putative or known effector genes: avrE1, hopM1, and hopAA1-1. Comparison of genomic sequences of DC3000, P. syringae pv. phaseolicola 1448A, and P. syringae pv. syringae B728a revealed that these are the only effector genes present in the CEL of all three strains. AvrEl was shown to carry functional TTSS translocation signals based on the performance of a fusion of the first 315 amino acids of AvrE1 to the Cya translocation reporter. A DC3000 delta avrE1 mutant was reduced in its ability to produce lesions but not in its ability to grow in host tomato leaves. AvrE1 expressed from the 35S promoter elicited cell death in nonhost Nicotiana tabacum leaves and host tomato leaves in Agrobacterium-mediated transient expression experiments. Mutations involving combinations of avrE1, hopM1, and hopAA1-1 revealed that deletion of both avrE1 and hopM1 reproduced the strongly reduced growth and lesion phenotype of the delta CEL mutant. Furthermore, quantitative assays involving different levels of inoculum and electrolyte leakage revealed that the avrE1/hopM1 and deltaCEL mutants both were partially impaired in their ability to elicit the hypersensitive response in nonhost N. benthamiana leaves. However, the avrE1/hopM1 mutant was not impaired in its ability to deliver AvrPto1(1-100)-Cya to nonhost N. benthamiana or host tomato leaves during the first 9 h after inoculation. These data suggest that AvrE1 acts within plant cells and promotes lesion formation and that the combined action of AvrE1 and HopM1 is particularly important in promoting bacterial growth in planta.

Cell Death↗
PubMed2026

GWAS Meta-analysis Identifies Novel Associated Loci and Points to Causal Tissues in Central Serous Chorioretinopathy.

OBJECTIVE: To define CSC genetic architecture and identify implicated ocular tissues, cell types, genes, and circulating proteins. DATA SOURCES: Genome-wide data were assembled from FinnGen, All of Us, Mass General Brigham Biobank, Million Veteran Program, and a Dutch chronic CSC cohort. Serum protein quantitative trait loci, human single-cell ocular atlases, and UK Biobank macular optical coherence tomography (OCT) imaging were used for downstream analyses. STUDY SELECTION: Five European-ancestry cohorts with genome-wide data and cohort-specific CSC case-control definitions were included, comprising 2,584 cases and 1,044,455 controls. Variants present in at least 2 cohorts were meta-analyzed. DATA EXTRACTION AND SYNTHESIS: Cohort-level GWASs were adjusted for age, age squared, sex, genotyping array or batch, and 10 genetic principal components, then combined using fixed-effects inverse-variance meta-analysis. Post-GWAS analyses included gene prioritization, colocalization, Mendelian randomization, single-cell disease-relevance scoring, and testing of a CSC genetic risk score in UK Biobank OCT images. MAIN OUTCOMES AND MEASURES: Genome-wide significant CSC loci, effector genes and proteins, tissue and cell-type enrichment, and CSC-relevant OCT abnormalities. RESULTS: Across 11,068,938 variants, 10 loci reached genome-wide significance (P < 5 &#xd7; 10-8), including 3 novel loci near TGFB1, LINC00551, and LOC105375630 and 7 replicated loci near CFH, CD46, NOTCH4, PREX1, PTPRB, GATA5, and TNFRSF10A. Integrative analyses prioritized 10 candidate effector genes. Colocalization and Mendelian randomization implicated circulating TNFRSF10A, TGFB1, and CASP10 levels. Single-cell analyses localized genetic risk to sclera (P = 2.0 &#xd7; 10-4) and vascular endothelial cells (P = 4.0 &#xd7; 10-4), with fibroblast enrichment. In UK Biobank, OCT abnormalities were more frequent in the top vs bottom 1% of CSC genetic risk (18 of 109 [16.5%] vs 8 of 134 [6.0%]; odds ratio, 4.05; 95% CI, 1.65-10.87; P = .002). CONCLUSIONS AND RELEVANCE: In this GWAS meta-analysis, CSC susceptibility localized predominantly to scleral and vascular biology rather than primary retinal pigment epithelial dysfunction. These findings support CSC as a sclerovascular disorder and nominate complement regulation, endothelial signaling, and extracellular matrix pathways for future study.

Journal Article↗
PubMed2026

Osteoarthritis Year in Review 2026: Genetics, genomics and epigenetics.

OBJECTIVE: The purpose of this narrative review is to highlight advances made over the past 12 months in the field of osteoarthritis (OA) genetics, genomics and epigenomics, with a particular focus on the interpretation of OA risk loci through functional genomic and regulatory approaches. DESIGN: PubMed and Europe PMC were searched to identify studies relevant to OA genetics, genomics and epigenomics published between 1st March 2025 and 30th April 2026. Searches used combinations of terms relating to genetics, genomics, epigenomics, functional genomics, molecular quantitative trait loci, chromatin accessibility and enhancer biology. Studies were limited to human subjects and English-language publications, with additional articles identified through citation screening and expert knowledge of the field. RESULTS: Over the past year, the field has continued to transition from large-scale locus discovery towards biological interpretation of OA genetic risk. Major advances included the largest OA genome-wide association study to date, further development of polygenic risk score approaches, and increasing integration of molecular quantitative trait loci, chromatin accessibility, and enhancer biology datasets to prioritise effector genes and elucidate regulatory mechanisms. Several studies highlighted the highly context-dependent nature of OA genetic risk mechanisms, demonstrating that distinct tissues, cell types, and regulatory layers can identify different candidate effector genes at the same locus. Additional developments included increasing application of singlecell and multi-omic technologies to study OA-relevant tissues. CONCLUSION: Recent advances in OA genetics have shifted the field from locus discovery towards mechanistic interpretation. Emerging evidence demonstrates that the biological consequences of genetic variation are highly dependent upon tissue, cell state and disease context, with different functional genomic approaches often prioritising distinct candidate genes and regulatory mechanisms at the same susceptibility locus. Together, these findings suggest that OA risk loci should increasingly be viewed as dynamic regulatory systems rather than simple variant-to-gene relationships, providing a framework for future studies aimed at resolving causal mechanisms, defining disease endotypes, and identifying therapeutic targets.

Genetics↗
PubMed2006

Engineering RNA interference-based resistance to dengue virus type 2 in genetically modified Aedes aegypti.

Mosquitoes (Aedes aegypti) were genetically modified to exhibit impaired vector competence for dengue type 2 viruses (DENV-2). We exploited the natural antiviral RNA interference (RNAi) pathway in the mosquito midgut by constructing an effector gene that expresses an inverted-repeat (IR) RNA derived from the premembrane protein coding region of the DENV-2 RNA genome. The A. aegypti carboxypeptidase A promoter was used to express the IR RNA in midgut epithelial cells after ingestion of a bloodmeal. The promoter and effector gene were inserted into the genome of a white-eye Puerto Rico Rexville D (Higgs' white eye) strain by using the nonautonomous mariner MosI transformation system. A transgenic family, Carb77, expressed IR RNA in the midgut after a bloodmeal. Carb77 mosquitoes ingesting an artificial bloodmeal containing DENV-2 exhibited marked reduction of viral envelope antigen in midguts and salivary glands after infection. DENV-2 titration of individual mosquitoes showed that most Carb77 mosquitoes poorly supported virus replication. Transmission in vitro of virus from the Carb77 line was significantly diminished when compared to control mosquitoes. The presence of DENV-2-derived siRNAs in RNA extracts from midguts of Carb77 and the loss of the resistance phenotype when the RNAi pathway was interrupted proved that DENV-2 resistance was caused by a RNAi response. Engineering of transgenic A. aegypti that show a high level of resistance against DENV-2 provides a powerful tool for developing population replacement strategies to control transmission of dengue viruses.

Aedes↗
PubMed1995

DNA fragmentation and activation of c-Jun in the cerebellum of mutant mice (weaver, Purkinje cell degeneration).

Weaver and Purkinje cell degeneration (pcd) are autosomal recessive mutations in the mouse characterized by an almost complete loss of cerebellar Purkinje neurones and granule cells, respectively. Developmental neuronal death occurs by activation of an apoptotic pathway and chromatin condensation has been observed in degenerating granule cells of weaver mutants. In the present study we demonstrate nuclear DNA fragmentation in Purkinje cells of pcd mice and in granule cells of weaver mutants during the period of neuronal degeneration using in situ end labelling by terminal transferase and fluorescein-dUTP. Furthermore, activation of candidate cell death effector gene c-jun has been detected exclusively within the affected cell populations by immunohistochemistry. Both labelled DNA fragments and nuclear c-Jun immunoreactivity were virtually absent in wild-type animals. Thus, genetically determined cell death in pcd and weaver mutant mice has features of apoptosis and may require activation of cell death effector genes.

Animals↗
PubMed1996

Characterization of a putative p53 binding site in the promoter of the mouse tissue inhibitor of metalloproteinases-3 (TIMP-3) gene: TIMP-3 is not a p53 target gene.

We have recently cloned the promoter of the mouse tissue inhibitor of metalloproteinases-3 (TIMP-3) gene and have identified a putative p53 binding site (5'-GGGCTTGCTT GACGTCCA GAACAGGGTC-3'), which contains two p53 consensus binding motifs (bold) with two nucleotide mismatches (underlined) in the second motif and an 8 bp spacer in between. Since both p53 and TIMP-3 are involved in cell cycle progression, we tested the hypothesis that TIMP-3 is a p53 downstream effector gene, mediating p53 activity. A good correlation between p53 protein levels and TIMP-3 expression was found among mouse liver cell lines. However, when TIMP-3 promoter driven luciferase constructs were tested for p53 responsiveness in these cells, the construct containing the putative p53 binding site did not show significant difference from the one having the p53 site deleted. The gel retardation assay showed that the oligo (T3) made from the putative p53 binding site in the mouse TIMP-3 promoter did not bind to p53 protein, nor did an oligo (T3W) with a correction for the two mismatched nucleotides in the second motif. When the 8 bp spacer was removed, however, the oligo T3WSF (same as the T3W with spacer free) but not T3SF (T3 without spacer) binds to p53, indicating that both the spacer between two motifs and consensus binding sites determined the p53 binding. It is worth noting that under a less stringent assay condition (0.2 microg instead of 1.0 microg of dI/dC), T3SF did weakly bind to p53. Lastly, the compounds that induce p53 transactivation activity did not induce TIMP-3 expression. We concluded from this study that TIMP-3 is not a p53 downstream effector gene.

Animals↗
PubMed2026

Effector loss and gain drives host range at a fitness cost.

Epidemic preparedness depends on tracking microbial evolution that drives shifts in ecological behaviors such as disease emergence. However, the genetic constraints mediating microbial emergence for generalist and specialist behaviors remain poorly described. Here, we addressed this question by combining comparative and functional genomics with phylogeny-based evolutionary analyses of the cereal pathogen Xanthomonas translucens. We show that a generalist X. translucens subgroup arose from a specialist ancestor, and the loss of a single effector gene, xopAL1, contributed to the generalist host expansion by promoting host jump from barley to wheat. Deleting barley-specialist X. translucens xopAL1 recapitulated the host jump to wheat and demonstrates risk across each globally distributed genetic lineage. However, this niche expansion via XopAL1 loss incurs a significant fitness cost to colonize barley. Moreover, the specialist lineage gained an additional effector gene, xopAJ, which enhanced virulence on barley while restricting oat infection, thereby reinforcing niche specialization. We further conducted transcriptomic analysis of wheat and determined that XopAL1 triggers a defense response that involves the reduction of photosynthetic processes. Our work provides an experimentally validated evolutionary framework to understand mechanisms of intergenera host jump. Overall, we demonstrate that single events of gene loss and gain shape ecological behaviors by creating a dynamic trade-off between niche breadth and specialization.

Triticum↗
PubMed2000

p53 protein oxidation in cultured cells in response to pyrrolidine dithiocarbamate: a novel method for relating the amount of p53 oxidation in vivo to the regulation of p53-responsive genes.

A novel method was developed to determine the oxidation status of proteins in cultured cells. Methoxy-polyethylene glycol-maleimide MW 2000 (MAL-PEG) was used to covalently tag p53 protein that was oxidized at cysteine residues in cultured cells. Treatment of MCF7 breast cancer cells with pyrrolidine dithiocarbamate (PDTC), a metal chelator, resulted in a minimum of 25% oxidation of p53. The oxidized p53 had an average of one cysteine residue oxidized per p53 protein molecule. The effect of PDTC treatment on downstream components of the p53 signal-transduction pathway was tested. PDTC treatment prevented actinomycin D-mediated up-regulation of two p53 effector gene products, murine double minute clone 2 oncoprotein and p21(WAF1/CIP1) (where WAF1 corresponds to wild-type p53-activated fragment 1 and CIP1 corresponds to cyclin-dependent kinase-interacting protein 1). Actinomycin D treatment led to accumulation of p53 protein in the nucleus. However, when cells were simultaneously treated with PDTC and actinomycin D, p53 accumulated in both the nucleus and the cytoplasm. The data indicate that an average of one cysteine residue per p53 protein molecule is highly sensitive to oxidation and that p53 can be efficiently oxidized by PDTC in cultured cells. PDTC-mediated oxidation of p53 correlates with altered p53 subcellular localization and reduced activation of p53 downstream effector genes. The novel method for detecting protein oxidation detailed in the present study may be used to determine the oxidation status of specific proteins in cells.

Animals↗
PubMed2001

Hepatitis C virus core protein modulates the interferon-induced transacting factors of Jak/Stat signaling pathway but does not affect the activation of downstream IRF-1 or 561 gene.

Hepatitis C virus (HCV) has a propensity to cause chronic infection, with a low proportion of patients exhibiting a sustained response to interferon-alpha (IFNalpha) therapy. An earlier report suggested that HCV inhibits IFNalpha-induced signal transduction through the Jak/Stat pathway by preventing the formation of the transacting factor ISGF3 complex, although the effect on downstream pathway and the specific viral protein responsible for inhibition of IFNalpha-mediated signal transduction were not elucidated. HCV core protein displays a number of intriguing functional properties and has been implicated in virus-mediated pathogenesis. In this study, we have analyzed the effect of core protein upon IFNalpha- or IFNgamma-induced regulation of the Jak/Stat signaling pathway. HCV core protein expression exhibited a reduced Stat1 expression in IFN-treated mammalian cells. A gel retardation assay suggested a reduced level of formation of the transacting factors, GAF and ISGF3, in IFN-treated cells. Further studies from protein expression and RNase protection assay revealed that the reduced level of GAF or ISGF3 formation could be attributed to modulation of Stat1 protein expression, an important player for innate immunity in host defense mechanism. However, these modulatory effects did not interfere with the activation of the downstream effector genes, IRF-1 and 561, in IFN-treated cells. Stable transfectants of cells after introduction of a plasmid DNA encoding both the structural and the nonstructural proteins of HCV also exhibited a similar effect. Taken together, these results suggest that although expression of the core protein alone or with other HCV proteins modulate transacting factors of Jak/Stat signaling pathway, expression of the downstream effector genes IRF-1 and 561 remains unaffected upon IFN treatment and may contribute to host defense mechanism.

DNA-Binding Proteins↗
PubMed2001

Neural induction takes a transcriptional twist.

Over the past decade, several molecules have been identified that influence neural cell fate in vertebrate embryos during gastrulation. The first neural inducers studied were proteins produced by dorsal mesoderm (the Spemann organizer); most of these proteins act by directly binding to and antagonizing the function of bone morphogenetic proteins (BMPs). Recent experiments have suggested that other secreted signals, such as Wnt and FGF, may neuralize ectoderm before organizer function by a different mechanism. Neural effector genes that mediate the response of ectoderm to secreted neuralizing signals have also been discovered. Interestingly, most of these newly identified neuralizing pathways continue the theme of BMP antagonism, but rather than antagonizing BMP protein function, they may neuralize tissue by suppressing Bmp expression. Down-regulation of Bmp expression in the prospective neural plate during gastrulation seems to be a shared feature of neural induction in vertebrate embryos. However, the signals used to accomplish this task seem to vary among vertebrates. Here, we will discuss the role of the recently identified secreted signals and neural effector genes in vertebrate neurogenesis.

Animals↗
PubMed2001

Transactivation-deficient p73alpha (p73Deltaexon2) inhibits apoptosis and competes with p53.

p73 has recently been identified as a structural and functional homolog of the tumor suppressor protein p53. Overexpression of p53 activates transcription of p53 effector genes, causes growth inhibition and induced apoptosis. We describe here the effects of a tumor-derived truncated transcript of p73alpha (p73Deltaexon2) on p53 function and on cell death. This transcript, which lacks the acidic N-terminus corresponding to the transactivation domain of p53, was initially detected in a neuroblastoma cell line. Overexpression of p73Deltaexon2 partially protects lymphoblastoid cells against apoptosis induced by anti-Fas antibody or cisplatin. By cotransfecting p73Deltaexon2 with wild-type p53 in the p53 null line Saos 2, we found that this truncated transcript reduces the ability of wild-type p53 to promote apoptosis. This anti-apoptotic effect was also observed when p73Deltaexon2 was co-transfected with full-length p73 (p73alpha). This was further substantiated by suppression of p53 transactivation of the effector gene p21/Waf1 in p73Deltaexon2 transfected cells and by inhibition of expression of a reporter gene under the control of the p53 promoter. Thus, this truncated form of p73 can act as a dominant-negative agent towards transactivation by p53 and p73alpha, highlighting the potential implications of these findings for p53 signaling pathway. Furthermore, we demonstrate the existence of a p73Deltaexon2 transcript in a very significant proportion (46%) of breast cancer cell lines. However, a large spectrum of normal and malignant tissues need to be surveyed to determine whether this transdominant p73 variant occurs in a tumor-specific manner.

Alternative Splicing↗
PubMed1996

Evidence for apoptotic cell death in the choroid plexus following focal cerebral ischemia.

Focal cerebral ischemia in rats subjected to middle cerebral artery (MCA) occlusion results in apoptotic DNA fragmentation and activation of putative cell death effector genes in neurons and functional impairment of the plexus choroideus. In the present study we investigated whether cerebral ischemia may induce apoptotic cell death in the choroid plexus. Using in situ end-labeling by terminal transferase and fluorescein-dUTP, nuclear DNA breaks were detected in the choroid plexus of the lateral ventricle of the ischemic hemisphere after 6 h but not after 1.5 h of MCA occlusion. Intense cytoplasmic immunostaining for pro-apoptotic Bax protein and moderate immunolabeling for Bcl-X was observed in the epithelium of the choroid plexus of the lateral and third ventricles. However, constitutive expression of Bax and Bcl-X proteins in the plexus choroideus did not change significantly following focal ischemia. Thus, cells of the choroid plexus may die by apoptosis after several hours of cerebral ischemia. Modulation of cell death effector genes of the bcl-2 family however, may not be required for apoptotic cell death to occur.

Animals↗
PubMed2004

Pharmacological and genetic modulation of Wnt-targeted Cre-Lox-mediated gene expression in colorectal cancer cells.

Wnt-targeted gene therapy has been proposed as a treatment for human colorectal cancer (CRC). The Cre-Lox system consists of methodology for enhancing targeted expression from tissue-specific or cancer-specific promoters. We analyzed the efficiency of Wnt-specific promoters as drivers of the Cre-mediated activity of a luciferase reporter gene or cell death effector gene in CRC cell lines in the presence and absence of two modulators of Wnt activity, sodium butyrate and lithium chloride. Butyrate is present in the colonic lumen after digestion of fiber-rich foods, whereas the colonic lumen is readily accessible to lithium chloride. In both SW620 and HCT-116 CRC cells, a physiologically relevant concentration of butyrate upregulated reporter and effector activity and altered the Wnt-specific expression pattern. Lithium chloride markedly enhanced Cre-Lox-mediated Wnt-specific reporter expression only in APC wild-type CRC cells. Possibilities for genetic modulation of the proposed CRC therapy included Wnt-specific expression of a floxed Lef1-VP16 fusion that enhanced Wnt-specific cell death and of a floxed dominant-negative Tcf4 that specifically downregulated endogenous Wnt activity. These findings demonstrated that the Cre-Lox system, in combination with pharmacological and genetic modulators, represents effective methodology for enhancing Wnt-targeted gene therapy.

Apoptosis↗
PubMed2004

The ABI2-dependent abscisic acid signalling controls HrpN-induced drought tolerance in Arabidopsis.

HrpN, a protein produced by the plant pathogenic bacterium Erwinia amylovora, has been shown to stimulate plant growth and resistance to pathogens and insects. Here we report that HrpN activates abscisic acid (ABA) signalling to induce drought tolerance (DT) in Arabidopsis thaliana L. plants grown with water stress. Spraying wild-type plants with HrpN-promoted stomatal closure decreased leaf transpiration rate, increased moisture and proline levels in leaves, and alleviated extents of damage to cell membranes and plant drought symptoms caused by water deficiency. In plants treated with HrpN, ABA levels increased; expression of several ABA-signalling regulatory genes and the important effector gene rd29B was induced or enhanced. Induced expression of rd29B, promotion of stomatal closure, and reduction in drought severity were observed in the abi1-1 mutant, which has a defect in the phosphatase ABI1, after HrpN was applied. In contrast, HrpN failed to induce these responses in the abi2-1 mutant, which is impaired in the phosphatase ABI2. Inhibiting wild-type plants to synthesize ABA eliminated the role of HrpN in promoting stomatal closure and reducing drought severity. Moreover, resistance to Pseudomonas syringae developed in abi2-1 as in wild-type plants following treatment with HrpN. Thus, an ABI2-dependent ABA signalling pathway is responsible for the induction of DT but does not affect pathogen defence under the circumstances of this study.

Abscisic Acid↗
PubMed1991

During Drosophila embryogenesis the beta 1 tubulin gene is specifically expressed in the nervous system and the apodemes.

We determined the in vivo distribution of the beta 1 tubulin from D. melanogaster using isotype specific antibodies. Maternally expressed beta 1 tubulin is incorporated into mitotic spindles. Later in development a strong expression in the CNS is observed. Furthermore, all chordotonal organs and the apodemes are marked by beta 1 tubulin. Nuclear run-on assays and stage specific in vitro transcription showed a zygotic expression of the beta 1 tubulin gene from the extended germ-band stage onwards. Using the P-element system, we identified several elements; upstream between -2.2 kb and the transcription initiation site, elements for low level expression in the CNS are present. In the intron between +0.44 kb and +2.5 kb enhancer elements are located that drive the expression in the chordotonal organs and the apodemes. Between the start site and +0.44 kb (273 bp) and +2.5 kb and the second exon (315 bp), maternal and CNS enhancers result in full level expression of a lacZ-beta 1 reporter gene. We show, that the beta 1 tubulin gene is very early effector gene starting its expression shortly after the commitment of neuroblast cell fate. This gene offers an excellent model system for the identification of neural and apodeme specific transcription factors.

Amino Acid Sequence↗
PubMed2002

Z-DNA-binding proteins can act as potent effectors of gene expression in vivo.

The role of Z-DNA-binding proteins in vivo is explored in yeast. A conformation-specific yeast one-hybrid system is made in which formation of Z-DNA is studied near a minimal promoter site where it can be stabilized by negative supercoiling in addition to protein binding. Experiments were carried out with a Z-DNA-binding protein domain from the editing enzyme, double-stranded RNA adenosine deaminase 1. In the one-hybrid system, the reporter gene is activated when a Z-DNA-specific binding domain is fused with an activation domain and expressed in vivo. Significantly, it was found that even in the absence of the activation domain there is substantial transcription of the reporter gene if the Z-DNA-binding protein is expressed in the cell. This result suggests that Z-DNA formation in the promoter region induced or stabilized by a Z-DNA-binding protein can act as a cis-element in gene regulation. Related results have been found recently when the human chromatin-remodeling system converts a segment of DNA in the promoter region of the human colony-stimulating factor 1 gene into the left-handed Z-conformation.

Adenosine Deaminase↗
PubMed2006

The Notch-effector HRT1 gene plays a role in glomerular development and patterning of the Xenopus pronephros anlagen.

Notch signaling has been shown to play a role in cell fate decisions in the Xenopus pronephros anlagen. Here, we show that the Xenopus Hairy-related transcription factor (HRT) gene XHRT1, and the Hairy/Enhancer of split (HES) genes Xhairy1, Xhairy2b, esr9 and esr10, have distinct restricted dynamic expression patterns during pronephros development, and that their expression is regulated by Notch. XHRT1, which is the earliest and strongest gene expressed in the pronephric region, is initially transcribed predominantly in the forming glomus, where it is downregulated by antisense morpholino oligonucleotide inhibition of xWT1. Later, it is activated in the most dorsoanterior part of the pronephros anlagen that gives rise to the proximal tubules. In agreement with this dynamic expression profile, we found that early activation of Notch favors glomus, whereas only later activation promotes proximal tubule formation. We show that, among the bHLH-O factors tested, only XHRT1 efficiently inhibits distal tubule and duct formation, and that only its translational inhibition causes a reduction of the expression of proximal tubule and glomus markers. Using domain swap experiments, we found that the XHRT1 C-terminal region is crucial for its activity. Together, our results provide evidence that XHRT1 plays an important role in glomerular development and early proximodistal patterning that is distinct from those of the other pronephric bHLH repressors.

Animals↗