The role of brinker in mediating the graded response to Dpp in early Drosophila embryos

Development ◽  
1999 ◽  
Vol 126 (15) ◽  
pp. 3323-3334 ◽  
Author(s):  
A. Jazwinska ◽  
C. Rushlow ◽  
S. Roth
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Gene Activation ◽  
Ectopic Expression ◽  
Intermediate Level ◽  
Graded Response ◽  
High Level ◽  
Drosophila Embryos ◽  
Novel Protein

Brinker (Brk), a novel protein with features of a transcriptional repressor, regulates the graded response to Decapentaplegic (Dpp) in appendage primordia of Drosophila. Here, we show that in the embryo brk also has differential effects on Dpp target genes, depending on the level of Dpp activity required for their activation. Low-level target genes, like dpp itself, tolloid and early zerknullt, show strong ectopic expression in ventrolateral regions of brk mutant embryos; intermediate-level target genes like pannier show weak ectopic expression, while high-level target genes like u-shaped and rhomboid are not affected. Ectopic target gene activation in the absence of brk is independent of Dpp, Tkv and Medea, indicating that Dpp signaling normally antagonizes brk's repression of these target genes. brk is expressed like short gastrulation (sog) in ventrolateral regions of the embryo abutting the dpp domain. Here, both brk and sog antagonize the antineurogenic activity of Dpp so that only in brk sog double mutants is the neuroectoderm completely deleted.

scholarly journals CHOP-Dependent Stress-Inducible Expression of a Novel Form of Carbonic Anhydrase VI

1999 ◽  
Vol 19 (1) ◽  
pp. 495-504 ◽  
Author(s):  
John Sok ◽  
Xiao-Zhong Wang ◽  
Nikoleta Batchvarova ◽  
Masahiko Kuroda ◽  
Heather Harding ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Target Gene ◽  
Target Genes ◽  
Direct Evidence ◽  
Nuclear Protein ◽  
Intracellular Form ◽  
Carbonic Anhydrase Vi ◽  
Responsive Element

ABSTRACT CHOP (also called GADD153) is a stress-inducible nuclear protein that dimerizes with members of the C/EBP family of transcription factors and was initially identified as an inhibitor of C/EBP binding to classic C/EBP target genes. Subsequent experiments suggested a role for CHOP-C/EBP heterodimers in positively regulating gene expression; however, direct evidence that this is the case has so far not been uncovered. Here we describe the identification of a positively regulated direct CHOP-C/EBP target gene, that encoding murine carbonic anhydrase VI (CA-VI). The stress-inducible form of the gene is expressed from an internal promoter and encodes a novel intracellular form of what is normally a secreted protein. Stress-induced expression of CA-VI is both CHOP and C/EBPβ dependent in that it does not occur in cells deficient in either gene. A CHOP-responsive element was mapped to the inducibleCA-VI promoter, and in vitro footprinting revealed binding of CHOP-C/EBP heterodimers to that site. Rescue of CA-VIexpression in c/ebpβ−/− cells by exogenous C/EBPβ and a shorter, normally inhibitory isoform of the protein known as LIP suggests that the role of the C/EBP partner is limited to targeting the CHOP-containing heterodimer to the response element and points to a preeminent role for CHOP in CA-VI induction during stress.

scholarly journals Identification of Autosomal Regions Involved in Drosophila Raf Function

Genetics ◽  
2000 ◽  
Vol 156 (2) ◽  
pp. 763-774 ◽  
Author(s):  
Willis Li ◽  
Elizabeth Noll ◽  
Norbert Perrimon
Keyword(s):  
Limb Development ◽  
Target Gene ◽  
Biological Function ◽  
Genetic Interaction ◽  
Ectopic Expression ◽  
Tor Signaling ◽  
Downstream Effector ◽  
Early Embryos ◽  
Genomic Regions

Abstract Raf is an essential downstream effector of activated p21Ras (Ras) in transducing proliferation or differentiation signals. Following binding to Ras, Raf is translocated to the plasma membrane, where it is activated by a yet unidentified “Raf activator.” In an attempt to identify the Raf activator or additional molecules involved in the Raf signaling pathway, we conducted a genetic screen to identify genomic regions that are required for the biological function of Drosophila Raf (Draf). We tested a collection of chromosomal deficiencies representing ∼70% of the autosomal euchromatic genomic regions for their abilities to enhance the lethality associated with a hypomorphic viable allele of Draf, DrafSu2. Of the 148 autosomal deficiencies tested, 23 behaved as dominant enhancers of Draf  Su2, causing lethality in Draf  Su2 hemizygous males. Four of these deficiencies identified genes known to be involved in the Drosophila Ras/Raf (Ras1/Draf) pathway: Ras1, rolled (rl, encoding a MAPK), 14-3-3ϵ, and bowel (bowl). Two additional deficiencies removed the Drosophila Tec and Src homologs, Tec29A and Src64B. We demonstrate that Src64B interacts genetically with Draf and that an activated form of Src64B, when overexpressed in early embryos, causes ectopic expression of the Torso (Tor) receptor tyrosine kinase-target gene tailless. In addition, we show that a mutation in Tec29A partially suppresses a gain-of-function mutation in tor. These results suggest that Tec29A and Src64B are involved in Tor signaling, raising the possibility that they function to activate Draf. Finally, we discovered a genetic interaction between Draf  Su2 and Df(3L)vin5 that revealed a novel role of Draf in limb development. We find that loss of Draf activity causes limb defects, including pattern duplications, consistent with a role for Draf in regulation of engrailed (en) expression in imaginal discs.

scholarly journals Low-affinity transcription factor binding sites shape morphogen responses and enhancer evolution

2013 ◽  
Vol 368 (1632) ◽  
pp. 20130018 ◽  
Author(s):  
Andrea I. Ramos ◽  
Scott Barolo
Keyword(s):  
Transcription Factor ◽  
Binding Affinity ◽  
Binding Sites ◽  
Target Genes ◽  
Gene Activation ◽  
Transcriptional Response ◽  
Morphogen Gradients ◽  
Weak Binding ◽  
Initial Hypothesis

In the era of functional genomics, the role of transcription factor (TF)–DNA binding affinity is of increasing interest: for example, it has recently been proposed that low-affinity genomic binding events, though frequent, are functionally irrelevant. Here, we investigate the role of binding site affinity in the transcriptional interpretation of Hedgehog (Hh) morphogen gradients . We noted that enhancers of several Hh-responsive Drosophila genes have low predicted affinity for Ci, the Gli family TF that transduces Hh signalling in the fly. Contrary to our initial hypothesis, improving the affinity of Ci/Gli sites in enhancers of dpp , wingless and stripe , by transplanting optimal sites from the patched gene, did not result in ectopic responses to Hh signalling. Instead, we found that these enhancers require low-affinity binding sites for normal activation in regions of relatively low signalling. When Ci/Gli sites in these enhancers were altered to improve their binding affinity, we observed patterning defects in the transcriptional response that are consistent with a switch from Ci-mediated activation to Ci-mediated repression. Synthetic transgenic reporters containing isolated Ci/Gli sites confirmed this finding in imaginal discs. We propose that the requirement for gene activation by Ci in the regions of low-to-moderate Hh signalling results in evolutionary pressure favouring weak binding sites in enhancers of certain Hh target genes.

Immunoglobulin heavy-chain enhancer is required to maintain transfected gamma 2A gene expression in a pre-B-cell line

1990 ◽  
Vol 10 (3) ◽  
pp. 1076-1083
Author(s):  
B Porton ◽  
D M Zaller ◽  
R Lieberson ◽  
L A Eckhardt
Keyword(s):  
B Cell ◽  
Cell Lines ◽  
Heavy Chain ◽  
Gene Activation ◽  
Immunoglobulin Heavy Chain ◽  
Transcription Unit ◽  
Enhancer Activity ◽  
Igh Genes ◽  
High Level

The immunoglobulin heavy-chain (IgH) enhancer serves to activate efficient and accurate transcription of cloned IgH genes when introduced into B lymphomas or myelomas. The role of this enhancer after gene activation, however, is unclear. The endogenous IgH genes in several cell lines, for example, have lost the IgH enhancer by deletion and yet continue to be expressed. This might be explained if the role of the enhancer were to establish high-level gene transcription but not to maintain it. Alternatively, other enhancers might lie adjacent to endogenous IgH genes, substituting their activity for that of the lost IgH enhancer. To address both of these alternatives, we searched for enhancer activity within the flanking regions of one of these IgH enhancer-independent genes and designed an experiment that allowed us to consider separately the establishment and maintenance of expression of a transfected gene. For the latter experiment we generated numerous pre-B cell lines stably transformed with a gamma 2a gene. In this gene, the IgH enhancer lay at a site outside the heavy-chain transcription unit, between DH and JH gene segments. After expression of the transfected gene was established, selective conditions were chosen for the outgrowth of subclones that had undergone D-J joining and thus IgH enhancer deletion. Measurements of gamma 2a expression before and after enhancer deletion revealed that the enhancer was required for maintenance of expression of the transfected gene. The implication of this finding for models of enhancer function in endogenous genes is discussed.

scholarly journals Transgenic Analysis Reveals that Thyroid Hormone Receptor Is Sufficient To Mediate the Thyroid Hormone Signal in Frog Metamorphosis

2004 ◽  
Vol 24 (20) ◽  
pp. 9026-9037 ◽  
Author(s):  
Daniel R. Buchholz ◽  
Akihiro Tomita ◽  
Liezhen Fu ◽  
Bindu D. Paul ◽  
Yun-Bo Shi
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Target Genes ◽  
Thyroid Hormone Receptor ◽  
Gene Activation ◽  
Inducible Promoter ◽  
Vertebrate Development ◽  
Transcription System

ABSTRACT Thyroid hormone (T3) has long been known to be important for vertebrate development and adult organ function. Whereas thyroid hormone receptor (TR) knockout and transgenic studies of mice have implicated TR involvement in mammalian development, the underlying molecular bases for the resulting phenotypes remain to be determined in vivo, especially considering that T3 is known to have both genomic, i.e., through TRs, and nongenomic effects on cells. Amphibian metamorphosis is an excellent model for studying the role of TR in vertebrate development because of its total dependence on T3. Here we investigated the role of TR in metamorphosis by developing a dominant positive mutant thyroid hormone receptor (dpTR). In the frog oocyte transcription system, dpTR bound a T3-responsive promoter and activated the promoter independently of T3. Transgenic expression of dpTR under the control of a heat shock-inducible promoter in premetamorphic tadpoles led to precocious metamorphic transformations. Molecular analyses showed that dpTR induced metamorphosis by specifically binding to known T3 target genes, leading to increased local histone acetylation and gene activation, similar to T3-bound TR during natural metamorphosis. Our experiments indicated that the metamorphic role of T3 is through genomic action of the hormone, at least on the developmental parameters tested. They further provide the first example where TR is shown to mediate directly and sufficiently these developmental effects of T3 in individual organs by regulating target gene expression in these organs.

scholarly journals Role of Gα12 and Gα13 as Novel Switches for the Activity of Nrf2, a Key Antioxidative Transcription Factor

2007 ◽  
Vol 27 (17) ◽  
pp. 6195-6208 ◽  
Author(s):  
Min Kyung Cho ◽  
Won Dong Kim ◽  
Sung Hwan Ki ◽  
Jong-Ik Hwang ◽  
Sangdun Choi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Target Gene ◽  
Target Genes ◽  
Gene Knockout ◽  
Serine Phosphorylation ◽  
Related Factor ◽  
Dependent Signal ◽  
Extracellular Stimuli ◽  
Target Gene Induction

ABSTRACT Gα12 and Gα13 function as molecular regulators responding to extracellular stimuli. NF-E2-related factor 2 (Nrf2) is involved in a protective adaptive response to oxidative stress. This study investigated the regulation of Nrf2 by Gα12 and Gα13. A deficiency of Gα12, but not of Gα13, enhanced Nrf2 activity and target gene transactivation in embryo fibroblasts. In mice, Gα12 knockout activated Nrf2 and thereby facilitated heme catabolism to bilirubin and its glucuronosyl conjugations. An oligonucleotide microarray demonstrated the transactivation of Nrf2 target genes by Gα12 gene knockout. Gα12 deficiency reduced Jun N-terminal protein kinase (JNK)-dependent Nrf2 ubiquitination required for proteasomal degradation, and so did Gα13 deficiency. The absence of Gα12, but not of Gα13, increased protein kinase C δ (PKC δ) activation and the PKC δ-mediated serine phosphorylation of Nrf2. Gα13 gene knockout or knockdown abrogated the Nrf2 phosphorylation induced by Gα12 deficiency, suggesting that relief from Gα12 repression leads to the Gα13-mediated activation of Nrf2. Constitutive activation of Gα13 promoted Nrf2 activity and target gene induction via Rho-mediated PKC δ activation, corroborating positive regulation by Gα13. In summary, Gα12 and Gα13 transmit a JNK-dependent signal for Nrf2 ubiquitination, whereas Gα13 regulates Rho-PKC δ-mediated Nrf2 phosphorylation, which is negatively balanced by Gα12.

Study on the Function of miRNA-155 Target Using Bioinformatics Methods

2013 ◽  
Vol 709 ◽  
pp. 858-861
Author(s):  
De Ming Han ◽  
Zi Jun Shen ◽  
Li Hui Zhao
Keyword(s):  
Protein Expression ◽  
Mirna Target ◽  
Target Gene ◽  
Target Genes ◽  
Gene Prediction ◽  
Diagnosis And Treatment ◽  
Transcriptional Level ◽  
Mirna Target Gene ◽  
Non Coding Rnas

MicroRNAs are small non-coding RNAs that act at the post-transcriptional level, regulating protein expression by repressing translation or destabilizing mRNA target. We searched information about miR-155 in miRBase. Target genes of miR-155 are predicted by four miRNA target gene prediction softwares. The result shows that miR-155 was involved in proliferation, differentiation and apoptosis. These results can contribute to further study on the role of microRNA in diagnosis and treatment of cancer.

scholarly journals MicroRNA-381 Negatively Regulates TLR4 Signaling in A549 Cells in Response to LPS Stimulation

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Zhihao Xu ◽  
Dapeng Dong ◽  
Xiaofei Chen ◽  
Huaqiong Huang ◽  
Shenglan Wen
Keyword(s):  
Target Gene ◽  
Target Genes ◽  
Bioinformatics Analysis ◽  
Respiratory Infections ◽  
A549 Cells ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Elisa Kit ◽  
Cox 2

It is widely reported that miR-381 is dysregulated in various tumors. However, the specific role of miR-381 in respiratory infections has not been reported. To probe this role, A549 cells were pretreated with 1 μg/mL LPS for 24 h. The level of miR-381 was detected using RT-qPCR. The expression of proinflammatory cytokines was determined using an ELISA kit and western blotting. Bioinformatics analysis was used to predict the target genes of miR-381, and a luciferase reporter assay was used to validate the expression of the target genes. miR-381 expression was increased in A549 cells treated with LPS, which is a ligand of TLRs. Further study revealed that the overexpression of miR-381 increased the activity of NF-κB signaling, thereby increasing the expression of IL-6, TNFα, and COX-2. Further study revealed that IκBα was a target gene of miR-381. The upregulation of miR-381 under LPS stimulation contributes to respiratory infections mainly by targeting IκBα.

scholarly journals Role of Active Efflux in Association with Target Gene Mutations in Fluoroquinolone Resistance in Clinical Isolates of Vibrio cholerae

2002 ◽  
Vol 46 (8) ◽  
pp. 2676-2678 ◽  
Author(s):  
Somesh Baranwal ◽  
Keya Dey ◽  
T. Ramamurthy ◽  
G. Balakrish Nair ◽  
Manikuntala Kundu
Keyword(s):  
Vibrio Cholerae ◽  
Target Gene ◽  
Target Genes ◽  
Gene Mutations ◽  
Proton Motive Force ◽  
Quinolone Resistance ◽  
Clinical Isolates ◽  
Fluoroquinolone Resistance ◽  
Active Efflux

ABSTRACT Quinolones are among the drugs of choice in the management of cholera caused by Vibrio cholerae. In this study, we demonstrate that, in addition to mutations detected in the target genes gyrA and parC, proton motive force-dependent efflux is involved in quinolone resistance in clinical isolates of V. cholerae.

scholarly journals Creating Biotechnological Hybrids of Sugar Beet

2019 ◽  
Vol 8 (6) ◽  
pp. 5167-5175 ◽  
Keyword(s):  
Gene Expression ◽  
Sugar Beet ◽  
Target Genes ◽  
Mendelian Segregation ◽  
Breeding Programs ◽  
Its Gene ◽  
Pair Mating ◽  
The Stability ◽  
High Level

Currently, implementation of the breeding programs, including the commonly recognized areas and classic breeding methods, cannot sufficiently ensure a quick and significant increase in the productivity of sugar beet hybrids, since its gene pool is almost exhausted. Based on the achievements in the field of genetics, new approaches to and opportunities in creating highly productive agrocoenoses of sugar beet have become popular. As a result of many years of work, results have been obtained about the nature of inheriting the resistance to glyphosate in individual heterozygous apo- and syncarpous forms in case of inbreeding and pair mating with the MC tester. The expression of target genes in the generations was monitored by the survival rate of sugar beet plants after the treatment with glyphosate. During the research, individuals with a high level of gene expression were selected. Upon self-pollination of initial heterozygous original forms, deviations from Mendelian segregation were observed in most cases. The criterion for assessing the stability of expression of glyphosate resistance genes in case of seed breeding was the compliance with the laws of Mendel among the analyzed descendants. In the initial stages of the research, the level of stability gene expression had been 10 – 15 % of the total number of analyzed plants. After four self-pollinations, the stability gene expression significantly increased, and genotypes with the resistance of 91 – 100 % were selected. The first apo- and syncarpous self-pollinating lines of sugar beet with high tolerance in the role of resistance donors have been created. The positive results of preliminary tests of the first glyphosate-tolerant hybrids need confirmation. Seeds and roots of resistant forms have been obtained for further research.

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