Regulation of a dpp target gene in the Drosophila embryo

Development ◽  
1997 ◽  
Vol 124 (2) ◽  
pp. 303-311 ◽  
Author(s):  
J. Rusch ◽  
M. Levine
Keyword(s):  
Target Gene ◽  
Fusion Gene ◽  
Drosophila Embryo ◽  
Specific Expression ◽  
Downstream Target ◽  
Embryonic Tissues ◽  
Posterior Midgut ◽  
Downstream Target Gene ◽  
Genetic Epistasis ◽  
Vp16 Fusion

In Drosophila, two TGF-beta growth factors, dpp and screw, function synergistically to subdivide the dorsal ectoderm into two embryonic tissues, the amnioserosa and dorsal epidermis. Previous studies have shown that peak dpp activity is required for the localized expression of zerknullt (zen), which encodes a homeodomain transcription factor. We present evidence that zen directly activates the amnioserosa-specific expression of a downstream target gene, Race (Related to angiotensin converting enzyme). A 533 bp enhancer from the Race promoter region is shown to mediate selective expression in the amnioserosa, as well as the anterior and posterior midgut rudiments. This enhancer contains three zen protein binding sites, and mutations in these sites virtually abolish the expression of an otherwise normal Race-lacZ fusion gene in the amnioserosa, but not in the gut. Genetic epistasis experiments suggest that zen is not the sole activator of Race, although a hyperactivated form of zen (a zen-VP16 fusion protein) can partially complement reduced levels of dpp activity. These results suggest that dpp regulates multiple transcription factors, which function synergistically to specify the amnioserosa.

The Regulation of Downstream Target Gene AP-2γ by Transcription Factor OCT-4

2013 ◽  
Vol 40 (1) ◽  
pp. 43
Author(s):  
Xiao-Meng ZHAO ◽  
Cheng WANG ◽  
Xiao-Feng LI ◽  
Xiao-Ting ZHANG ◽  
Xi-Zhi LIU ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Target Gene ◽  
Downstream Target ◽  
Downstream Target Gene

Aryl Hydrocarbon Receptor: Its Regulation and Roles in Transformation and Tumorigenesis

2019 ◽  
Vol 20 (6) ◽  
pp. 625-634 ◽  
Author(s):  
Xun Che ◽  
Wei Dai
Keyword(s):  
Target Gene ◽  
Tumor Development ◽  
Environmental Response ◽  
Carcinogenic Effect ◽  
Post Translational Modifications ◽  
Downstream Target ◽  
Aryl Hydrocarbon ◽  
Downstream Target Gene ◽  
Major Mediator

AhR is an environmental response gene that mediates cellular responses to a variety of xenobiotic compounds that frequently function as AhR ligands. Many AhR ligands are classified as carcinogens or pro-carcinogens. Thus, AhR itself acts as a major mediator of the carcinogenic effect of many xenobiotics in vivo. In this concise review, mechanisms by which AhR trans-activates downstream target gene expression, modulates immune responses, and mediates malignant transformation and tumor development are discussed. Moreover, activation of AhR by post-translational modifications and crosstalk with other transcription factors or signaling pathways are also summarized.

Abstract 355: Exercise Prevents Doxorubicin-induced Cardiotoxicity via Targeting Microrna-669a-5p in Mice

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Yihua Bei ◽  
Jiahong Xu ◽  
Tianzhao Xu ◽  
Ping Chen ◽  
Lin Che ◽  
...  
Keyword(s):  
Protective Effect ◽  
Target Gene ◽  
Contractile Function ◽  
Cardiac Contractile Function ◽  
Downstream Target ◽  
Cardiac Contractile ◽  
Downstream Target Gene ◽  
Cardiac Ejection Fraction ◽  
Response To Exercise ◽  
Fractional Shortening

Doxorubicin (Dox)-induced cardiotoxicity, usually associated with increased oxidative stress, myofibrillar deterioration, and impaired cardiac contractile function, is a serious complication of antitumor therapy which may not be detected for many years. Growing evidence indicates that the regulation of cardiac microRNA (miRNA, miR) in response to exercise is essentially involved in the protective effect of exercise in the treatment of cardiovascular diseases. However, it is largely unknown whether and how exercise could prevent Dox-induced cardiotoxicity via regulating miRNA biology. In the current study, C57BL/6 mice were either subjected to a 3-week swimming program or remained sedentary. Mice were then treated with Dox (ip. 4 mg/kg/week for 4 weeks) to induce cardiotoxicity. Our data demonstrated that Dox resulted in marked reduction of cardiac ejection fraction (EF, %) and fractional shortening (FS, %) as measured by echocardiography. Interestingly, exercise significantly improved cardiac EF (%) and FS (%) in Dox-treated mice, indicating the protective effect of exercise in Dox-induced cardiotoxicity. Then, we performed microarray analysis (Affymetrix 3.0) showing that miR-27a-5p, miR-34b-3p, miR-185-3p, miR-203-3p, miR-669a-5p, miR-872-3p, and let-7i-3p were significantly reduced, while miR-2137 was increased in the hearts of exercised Dox-treated mice versus sedentary Dox-treated mice (FC(abs)>1.5, p<0.05). Using qRT-PCR, we further verified that miR-669a-5p was reduced by exercise training in Dox-treated mice. These data reveal that miR-669a-5p might be a potential miRNA mimicking the benefit of exercise in Dox-induced cardiotoxicity. Further study is needed to clarify the functional effect of miR-669a-5p and to identify its downstream target gene that contributes to the prevention and treatment of Dox-induced cardiotoxicity.

scholarly journals MicroRNA-346 inhibits the growth of glioma by directly targeting NFIB

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yangyang Li ◽  
Jia Xu ◽  
Jiale Zhang ◽  
Jie Zhang ◽  
Jian Zhang ◽  
...  
Keyword(s):  
Target Gene ◽  
Glioma Cells ◽  
Downstream Target ◽  
Downstream Target Gene ◽  
Direct Target ◽  
Proliferation Assays ◽  
The Relationship ◽  
Proliferation In Vitro

Abstract Background Glioma is considered one of the most common tumors and has a poor prognosis. Recently, microRNAs (miRNAs) have been reported to be strongly linked to various human tumors including glioma. In this study, we investigated a new anticancer miRNA, miR-346, to determine the effects and mechanism of miR-346 and its downstream target gene NFIB on tumors. Methods Lentivirus transfection, real-time PCR, western blotting, immunohistochemistry, cell proliferation assays, and mouse experiments were used to examine the relationship between miR-346 and its regulation of NFIB in glioma cells. Results The expression of miR-346 was downregulated in glioma cells. Overexpression of miR-346 arrested the cell cycle of glioma cells and inhibited their proliferation in vitro and in vivo. NFIB was a direct target of miR-346, whose expression was reduced by the miRNA. Overexpression of NFIB reversed all tested functions of miR-346. Conclusion miR-346 inhibited the growth of glioma cells by targeting NFIB and may be a new prognostic and diagnostic biomarker for glioma.

scholarly journals LncRNA ADAMTS9-AS2 in osteosarcoma inhibits cell proliferation and enhances paclitaxel sensitivity by suppressing microRNA-130a-5p

2020 ◽  
Vol 18 ◽  
pp. 205873922093456 ◽  
Author(s):  
Xiaoqiang Ren ◽  
Jingwei Cai ◽  
Yongheng Wang ◽  
Xingren Zhu ◽  
Jun Qian ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Noncoding Rna ◽  
Target Gene ◽  
Luciferase Reporter ◽  
Critical Function ◽  
Downstream Target ◽  
Downstream Target Gene ◽  
Proliferation Ability ◽  
Polymerase Chain ◽  
Qpcr Experiment

Introduction: Long noncoding RNA ADAMTS9-AS2 (lncRNA ADAMTS9-AS2) has critical function in tumor growth and drug resistance of various cancers. However, the role and mechanism of lncRNA ADAMTS9-AS2 in osteosarcoma (OS) is still unclear. Methods: The expression of lncRNA ADAMTS9-AS2 and MicroRNAs-130a-5p (miR-130a-5p) was detected by real-time polymerase chain reaction (RT-qPCR) experiment. In addition, we used the plasmids transfection to construct the lncRNA ADAMTS9-AS2 overexpressed OS cell lines. Subsequently, the cell proliferation ability and the sensitivity to paclitaxel (PTX) in OS cells upon up-regulating lncRNA ADAMTS9-AS2 expression were analyzed via CCK-8 assay, while Western blotting experiment was performed to detect the regulatory mechanism. Results: We found that lncRNA ADAMTS9-AS2 was down-regulated in OS tissues, and the OS patients with lncRNA ADAMTS9-AS2 downexprssion were usually accompanied with a poor prognosis. Subsequently, we discovered that up-regulation of lncRNA ADAMTS9-AS2 inhibited cell proliferation and increased the sensitivity to PTX in OS cells. Interestingly, the Western blot results showed that overexpression of lncRNA ADAMTS9-AS2 could lead to PTEN expression increased, with PI3K and p-AKT expression decreased, indicating that lncRNA ADAMTS9-AS2 could increase the OS cell sensitivity to PTX via regulating PTEN-PI3K/AKT pathway. Furthermore, we identified MicroRNAs-130a-5p (miR-130a-5p) as the downstream target gene of lncRNA ADAMTS9-AS2, which was further confirmed by the luciferase reporter assay. More importantly, our data revealed that miR-130a-5p mimics could partly reverse the influence on cell proliferation and drug sensitivity induced by lncRNA ADAMTS9-AS2 overexpression. Conclusion: LncRNA ADAMTS9-AS2 exerts its anti-carcinogenesis function by sponging miR-130a-5p, which might be a new therapeutic target for OS treatment.

scholarly journals Amine Oxidase Copper-containing 1 (AOC1) Is a Downstream Target Gene of the Wilms Tumor Protein, WT1, during Kidney Development

2014 ◽  
Vol 289 (35) ◽  
pp. 24452-24462 ◽  
Author(s):  
Karin M. Kirschner ◽  
Julian F.W. Braun ◽  
Charlotte L. Jacobi ◽  
Lucas J. Rudigier ◽  
Anja Bondke Persson ◽  
...  
Keyword(s):  
Target Gene ◽  
Kidney Development ◽  
Wilms Tumor ◽  
Amine Oxidase ◽  
Downstream Target ◽  
Downstream Target Gene

scholarly journals Tmem178 acts in a novel negative feedback loop targeting NFATc1 to regulate bone mass

2015 ◽  
Vol 112 (51) ◽  
pp. 15654-15659 ◽  
Author(s):  
Corinne E. Decker ◽  
Zhengfeng Yang ◽  
Ryan Rimer ◽  
Kyung-Hyun Park-Min ◽  
Claudia Macaubas ◽  
...  
Keyword(s):  
Bone Loss ◽  
Feedback Loop ◽  
Target Gene ◽  
Transmembrane Protein ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Osteoclast Formation ◽  
Activated T Cells ◽  
Downstream Target ◽  
Skeletal Mass ◽  
Downstream Target Gene

Phospholipase C gamma-2 (PLCγ2)-dependent calcium (Ca2+) oscillations are indispensable for nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) activation and downstream gene transcription driving osteoclastogenesis during skeletal remodeling and pathological bone loss. Here we describe, to our knowledge, the first known function of transmembrane protein 178 (Tmem178), a PLCγ2 downstream target gene, as a critical modulator of the NFATc1 axis. In surprising contrast to the osteopetrotic phenotype of PLCγ2−/− mice, Tmem178−/− mice are osteopenic in basal conditions and are more susceptible to inflammatory bone loss, owing to enhanced osteoclast formation. Mechanistically, Tmem178 localizes to the ER membrane and regulates RANKL-induced Ca2+ fluxes, thus controlling NFATc1 induction. Importantly, down-regulation of Tmem178 is observed in human CD14+ monocytes exposed to plasma from systemic juvenile idiopathic arthritis patients. Similar to the mouse model, reduced Tmem178 expression in human cells correlates with excessive osteoclastogenesis. In sum, these findings identify an essential role for Tmem178 to maintain skeletal mass and limit pathological bone loss.

scholarly journals Integrative analysis of 10,000 epigenomic maps across 800 samples for regulatory genomics and disease dissection

2019 ◽  
Author(s):  
Carles B. Adsera ◽  
Yongjin P. Park ◽  
Wouter Meuleman ◽  
Manolis Kellis
Keyword(s):  
High Resolution ◽  
Genetic Variants ◽  
Complex Traits ◽  
Target Gene ◽  
Activity Patterns ◽  
Complex Trait ◽  
Contributing Factors ◽  
Downstream Target ◽  
Downstream Target Gene ◽  
Upstream Regulators

AbstractTo help elucidate genetic variants underlying complex traits, we develop EpiMap, a compendium of 833 reference epigenomes across 18 uniformly-processed and computationally-completed assays. We define chromatin states, high-resolution enhancers, activity patterns, enhancer modules, upstream regulators, and downstream target gene functions. We annotate 30,247 genetic variants associated with 534 traits, recognize principal and partner tissues underlying each trait, infer trait-tissue, tissue-tissue and trait-trait relationships, and partition multifactorial traits into their tissue-specific contributing factors. Our results demonstrate the importance of dense, rich, and high-resolution epigenomic annotations for complex trait dissection, and yield numerous new insights for understanding the molecular basis of human disease.

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