scholarly journals PPARGin Human Adipogenesis: Differential Contribution of Canonical Transcripts and Dominant Negative Isoforms

PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
M. Aprile ◽  
M. R. Ambrosio ◽  
V. D'Esposito ◽  
F. Beguinot ◽  
P. Formisano ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Human Mesenchymal Stem Cells ◽  
Dominant Negative ◽  
Differential Impact ◽  
Specific Expression ◽  
Specific Expression Pattern ◽  
Time Specific ◽  
First Time ◽  
Differential Contribution ◽  
Rule Out

The nuclear receptor PPARγis a key regulator of adipogenesis, and alterations of its function are associated with different pathological processes related to metabolic syndrome. We recently identified twoPPARGtranscripts encoding dominant negative PPARγisoforms. The existence of differentPPARGvariants suggests that alternative splicing is crucial to modulate PPARγfunction, underlying some underestimated aspects of its regulation. Here we investigatePPARGexpression in different tissues and cells affected in metabolic syndrome and, in particular, during adipocyte differentiation of human mesenchymal stem cells. We defined the transcript-specific expression pattern ofPPARGvariants encoding both canonical and dominant negative isoforms and identified a novelPPARGtranscript,γ1ORF4. Our analysis indicated that, during adipogenesis, the transcription of alternativePPARGvariants is regulated in a time-specific manner through differential usage of distinct promoters. In addition, our analysis describes—for the first time—the differential contribution of three ORF4 variants to this process, suggesting a still unexplored role for these dominant negative isoforms during adipogenesis. Therefore, our results highlight crucial aspects ofPPARGregulation, suggesting the need of further investigation to rule out the differential impact of allPPARGtranscripts in both physiologic and pathologic conditions, such as metabolism-related disorders.

scholarly journals Tissue and time specific expression pattern of interferon regulated genes in the chicken

BMC Genomics ◽  
2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Susanne Röll ◽  
Stefan Härtle ◽  
Thomas Lütteke ◽  
Bernd Kaspers ◽  
Sonja Härtle
Keyword(s):  
Expression Pattern ◽  
Specific Expression ◽  
Specific Expression Pattern ◽  
Time Specific

scholarly journals MiRNA Expression in Neuroendocrine Neoplasms of Frequent Localizations

2021 ◽  
Vol 7 (3) ◽  
pp. 38
Author(s):  
Alexandra Korotaeva ◽  
Danzan Mansorunov ◽  
Natalya Apanovich ◽  
Anna Kuzevanova ◽  
Alexander Karpukhin
Keyword(s):  
Mirna Expression ◽  
Malignant Tumors ◽  
Neuroendocrine Neoplasms ◽  
Specific Expression ◽  
Clinical Biomarkers ◽  
Different Types ◽  
Functional Features ◽  
First Time ◽  
Potential Biomarkers

Neuroendocrine neoplasms (NEN) are infrequent malignant tumors of a neuroendocrine nature that arise in various organs. They occur most frequently in the lungs, intestines, stomach and pancreas. Molecular diagnostics and prognosis of NEN development are highly relevant. The role of clinical biomarkers can be played by microRNAs (miRNAs). This work is devoted to the analysis of data on miRNA expression in NENs. For the first time, a search for specificity or a community of their functional characteristics in different types of NEN was carried out. Their properties as biomarkers were also analyzed. To date, more than 100 miRNAs have been characterized as differentially expressed and significant for the development of NEN tumors. Only about 10% of the studied miRNAs are expressed in several types of NEN; differential expression of the remaining 90% was found only in tumors of specific localizations. A significant number of miRNAs have been identified as potential biomarkers. However, only a few miRNAs have values that characterized their quality as markers. The analysis demonstrates the predominant specific expression of miRNA in each studied type of NEN. This indicates that miRNA’s functional features are predominantly influenced by the tissue in which they are formed.

scholarly journals Disrupting the LINC complex by AAV mediated gene transduction prevents progression of Lamin induced cardiomyopathy

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ruth Jinfen Chai ◽  
Hendrikje Werner ◽  
Peter Yiqing Li ◽  
Yin Loon Lee ◽  
Khaing Thet Nyein ◽  
...  
Keyword(s):  
Cardiac Failure ◽  
Viral Vector ◽  
Nuclear Periphery ◽  
Dominant Negative ◽  
Gene Transduction ◽  
Linc Complex ◽  
Specific Expression ◽  
Common Cause ◽  
Complex Protein ◽  
One Year

AbstractMutations in the LaminA gene are a common cause of monogenic dilated cardiomyopathy. Here we show that mice with a cardiomyocyte-specific Lmna deletion develop cardiac failure and die within 3–4 weeks after inducing the mutation. When the same Lmna mutations are induced in mice genetically deficient in the LINC complex protein SUN1, life is extended to more than one year. Disruption of SUN1’s function is also accomplished by transducing and expressing a dominant-negative SUN1 miniprotein in Lmna deficient cardiomyocytes, using the cardiotrophic Adeno Associated Viral Vector 9. The SUN1 miniprotein disrupts binding between the endogenous LINC complex SUN and KASH domains, displacing the cardiomyocyte KASH complexes from the nuclear periphery, resulting in at least a fivefold extension in lifespan. Cardiomyocyte-specific expression of the SUN1 miniprotein prevents cardiomyopathy progression, potentially avoiding the necessity of developing a specific therapeutic tailored to treating each different LMNA cardiomyopathy-inducing mutation of which there are more than 450.

Identification and expression analysis of Dazl homologue in Cynops cyanurus

Zygote ◽  
2021 ◽  
pp. 1-6
Author(s):  
Yinjiao Zhao ◽  
Ya Du ◽  
Qinglan Ge ◽  
Fang Yan ◽  
Shu Wei
Keyword(s):  
Phylogenetic Analysis ◽  
Comparative Studies ◽  
Rna Binding ◽  
Rna Binding Protein ◽  
Rna Recognition Motif ◽  
Rna Recognition ◽  
Specific Expression ◽  
Recognition Motif ◽  
Deleted In Azoospermia ◽  
Specific Expression Pattern

Summary The Dazl (deleted in azoospermia-like) gene encodes an RNA-binding protein containing an RNA recognition motif (RRM) and a DAZ motif. Dazl is essential for gametogenesis in vertebrates. In this study, we report the cloning of Dazl cDNA from Cynops cyanurus. Ccdazl mRNA showed a germline-specific expression pattern as expected. Ccdazl expression gradually decreased during oogenesis, suggesting that it may be involved in oocyte development. Phylogenetic analysis revealed that the Ccdazl protein shares conserved motifs/domains with Dazl proteins from other species. Cloning of Ccdazl provides a new tool to carry out comparative studies of germ cell development in amphibians.

scholarly journals Neuroendocrine prostate cancer has distinctive, non-prostatic HOX code that is represented by the loss of HOXB13 expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Siyuan Cheng ◽  
Shu Yang ◽  
Yingli Shi ◽  
Runhua Shi ◽  
Yunshin Yeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Hox Genes ◽  
Human Cancer ◽  
Specific Expression ◽  
Hox Gene ◽  
Human Cancer Cell Lines ◽  
All Trans Retinoic Acid ◽  
Neuroendocrine Prostate Cancer ◽  
Hox Code ◽  
Specific Expression Pattern

AbstractHOX gene-encoded homeobox proteins control body patterning during embryonic development; the specific expression pattern of HOX genes may correspond to tissue identity. In this study, using RNAseq data of 1019 human cancer cell lines that originated from 24 different anatomic sites, we established HOX codes for various types of tissues. We applied these HOX codes to the transcriptomic profiles of prostate cancer (PCa) samples and found that the majority of prostate adenocarcinoma (AdPCa) samples sustained a prostate-specific HOX code whereas the majority of neuroendocrine prostate cancer (NEPCa) samples did not, which reflects the anaplastic nature of NEPCa. Also, our analysis showed that the NEPCa samples did not correlate well with the HOX codes of any other tissue types, indicating that NEPCa tumors lose their prostate identities but do not gain new tissue identities. Additionally, using immunohistochemical staining, we evaluated the prostatic expression of HOXB13, the most prominently changed HOX gene in NEPCa. We found that HOXB13 was expressed in both benign prostatic tissues and AdPCa but its expression was reduced or lost in NEPCa. Furthermore, we treated PCa cells with all trans retinoic acid (ATRA) and found that the reduced HOXB13 expression can be reverted. This suggests that ATRA is a potential therapeutic agent for the treatment of NEPCa tumors by reversing them to a more treatable AdPCa.

scholarly journals Intestinal Apolipoprotein A-IV Gene Transcription Is Controlled by Two Hormone-Responsive Elements: A Role for Hepatic Nuclear Factor-4 Isoforms

2005 ◽  
Vol 19 (9) ◽  
pp. 2320-2334 ◽  
Author(s):  
Amena Archer ◽  
Dominique Sauvaget ◽  
Valérie Chauffeton ◽  
Pierre-Etienne Bouchet ◽  
Jean Chambaz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transgenic Mice ◽  
Distal Region ◽  
Proximal Region ◽  
Dominant Negative ◽  
Specific Expression ◽  
Nuclear Factors ◽  
Dominant Negative Form ◽  
Responsive Element ◽  
Hormone Responsive Element

Abstract In the small intestine, the expression of the apolipoprotein (apo) C-III and A-IV genes is restricted to the enterocytes of the villi. We have previously shown that, in transgenic mice, specific expression of the human apo C-III requires a hormone-responsive element (HRE) located in the distal region of the human apoA-IV promoter. This HRE binds the hepatic nuclear factors (HNF)-4α and γ. Here, intraduodenal injections in mice and infections of human enterocytic Caco-2/TC7 cells with an adenovirus expressing a dominant-negative form of HNF-4α repress the expression of the apoA-IV gene, demonstrating that HNF-4 controls the apoA-IV gene expression in enterocytes. We show that HNF-4α and γ functionally interact with a second HRE present in the proximal region of the human apoA-IV promoter. New sets of transgenic mice expressing mutated forms of the promoter, combined with the human apo C-III enhancer, demonstrate that, whereas a single HRE is sufficient to reproduce the physiological cephalo-caudal gradient of apoA-IV gene expression, both HREs are required for expression that is restricted to villi. The combination of multiple HREs may specifically recruit regulatory complexes associating HNF-4 and either coactivators in villi or corepressors in crypts.

Cdk5 mediates changes in morphology and promotes apoptosis of astrocytoma cells in response to heat shock

2001 ◽  
Vol 114 (6) ◽  
pp. 1145-1153 ◽  
Author(s):  
C. Gao ◽  
S. Negash ◽  
H.S. Wang ◽  
D. Ledee ◽  
H. Guo ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cell Line ◽  
Fluorescent Protein ◽  
Morphological Changes ◽  
Normal Growth ◽  
Dominant Negative ◽  
Specific Expression ◽  
Cell Matrix ◽  
Dominant Negative Mutation ◽  
U373 Cells

The cyclin-dependent kinase member, Cdk5, is expressed in a variety of cell types, but neuron-specific expression of its activator, p35, is thought to limit its activity to neurons. Here we demonstrate that both Cdk5 and p35 are expressed in the human astrocytoma cell line, U373. Cdk5 and p35 are present in the detergent-insoluble cytoskeletal fraction of this cell line and Cdk5 localizes to filopodia and vinculin-rich regions of cell-matrix contact in lamellopodia. When exposed to a 46(o)C heat shock, U373 cells change shape, lose cell-matrix contacts and show increased levels of apoptosis. To test whether Cdk5 activation might play a role in these events, U373 cells were stably transfected with histidine-tagged or green fluorescent protein-tagged constructs of Cdk5 or a dominant negative mutation, Cdk5T33. Under normal growth conditions, growth characteristics of the stably transfected lines were indistinguishable from untransfected U373 cells and Cdk5 localization was not changed. However, when subjected to heat shock, cells stably transfected with Cdk5-T33 remained flattened, showed little loss of cell-matrix adhesion, and exhibited significantly lower levels of apoptosis. In contrast, cells that overexpressed wild-type Cdk5 showed morphological changes similar to those seen in untransfected U373 cells in response to heat shock and had significantly higher levels of apoptosis. Heat-shocked cells showed changes in p35 mobility and stability of the Cdk5/p35 complex consistent with endogenous Cdk5 activity. Together these findings suggest that endogenous Cdk5 activity may play a key role in regulating morphology, attachment, and apoptosis in U373 cells, and raise the possibility that Cdk5 may be a general regulator of cytoskeletal organization and cell adhesion in both neuronal and non-neuronal cells.

scholarly journals Tissue Distribution of ACE2 Protein in Syrian Golden Hamster (Mesocricetus auratus) and Its Possible Implications in SARS-CoV-2 Related Studies

2021 ◽  
Vol 11 ◽  
Author(s):  
Voddu Suresh ◽  
Deepti Parida ◽  
Aliva P. Minz ◽  
Manisha Sethi ◽  
Bhabani S. Sahoo ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Golden Hamster ◽  
Expression Patterns ◽  
Mesocricetus Auratus ◽  
Syrian Golden Hamster ◽  
Surface Epithelium ◽  
Specific Expression ◽  
Tissue Specific ◽  
Tissue Specific Expression ◽  
Specific Expression Pattern

The Syrian golden hamster (Mesocricetus auratus) has recently been demonstrated as a clinically relevant animal model for SARS-CoV-2 infection. However, lack of knowledge about the tissue-specific expression pattern of various proteins in these animals and the unavailability of reagents like antibodies against this species hampers these models’ optimal use. The major objective of our current study was to analyze the tissue-specific expression pattern of angiotensin-converting enzyme 2, a proven functional receptor for SARS-CoV-2 in different organs of the hamster. Using two different antibodies (MA5-32307 and AF933), we have conducted immunoblotting, immunohistochemistry, and immunofluorescence analysis to evaluate the ACE2 expression in different tissues of the hamster. Further, at the mRNA level, the expression of Ace2 in tissues was evaluated through RT-qPCR analysis. Both the antibodies detected expression of ACE2 in kidney, small intestine, tongue, and liver. Epithelium of proximal tubules of kidney and surface epithelium of ileum expresses a very high amount of this protein. Surprisingly, analysis of stained tissue sections showed no detectable expression of ACE2 in the lung or tracheal epithelial cells. Similarly, all parts of the large intestine were negative for ACE2 expression. Analysis of tissues from different age groups and sex didn’t show any obvious difference in ACE2 expression pattern or level. Together, our findings corroborate some of the earlier reports related to ACE2 expression patterns in human tissues and contradict others. We believe that this study’s findings have provided evidence that demands further investigation to understand the predominant respiratory pathology of SARS-CoV-2 infection and disease.

scholarly journals Genome-wide analysis of CrRLK1L genes and their expression profiling during fiber development in cotton

2020 ◽  
Author(s):  
Dongyun Zuo ◽  
Javaria Ashraf ◽  
Hailiang Cheng ◽  
Shang Liu ◽  
Youping Zhang ◽  
...  
Keyword(s):  
Stress Responses ◽  
Plant Immunity ◽  
Fiber Development ◽  
The Other ◽  
Element Analysis ◽  
Specific Expression ◽  
Group Iii ◽  
Group I ◽  
Genome Wide ◽  
Specific Expression Pattern

Abstract Background: Catharanthus roseus receptor-like kinase 1-like (CrRLK1Ls) proteins play important roles in cell growth, plant morphogenesis, reproduction, hormone signaling, plant immunity and stress responses in Arabidopsis. However, not much information is available about their functions during cotton fiber development.Results: We identified a total of 125, 73 and 71 full-length putative CrRLK1L genes in G. hirsutum, G. arboreum and G. raimondii, which are much greater than that of the other plants. The phylogenetic and gene structure analysis divided the cotton CrRLK1L genes into six major groups, among which only group I and II contained AtCrRLK1Ls of Arabidopsis, suggesting that other groups (group III-VI) were expanded by gene duplication during cotton evolution. Genome collinearity analysis revealed that half of the At02 genes in G. hirsutum derived from A02 of G. arboreum, while the other half (GhCrRLK1L6 and GhCrRLK1L7) originated from Dt03 and Dt02 of G. raimondii, indicating segmental duplication between noncorresponding chromosomes during polyploidization of G. hirsutum. In addition, expression and cis-element analysis revealed that only 22 GhCrRLK1Ls showed specific expression pattern during fiber development which are mainly due to the presence of binding sites for NAC, MYB and WRKY transcription factors.Conclusions: This study provides a strong foundation to further explore the molecular mechanism of CrRLK1L genes during fiber development in upland cotton.

scholarly journals Identification and Functional Characterization of the CVOMT and EOMT Genes Promoters from Ocimum Basilicum L

2021 ◽  
Author(s):  
Fatemeh Khakdan ◽  
Zahra Shirazi ◽  
Mojtaba Ranjbar
Keyword(s):  
Water Deficit ◽  
Transcriptional Control ◽  
Functional Characterization ◽  
Pcr Analysis ◽  
Water Deficit Stress ◽  
Specific Expression ◽  
Stress Dependent ◽  
First Time ◽  
Dependent Mechanism

Abstract Methyl chavicol and methyl eugenol are important phenylpropanoid compounds previously purified from basil. These compounds are significantly enhanced by the water deficit stress-dependent mechanism. Here, for the first time, pObCVOMT and pObEOMT promoters were extracted by the genome walking method. They were then cloned into the upstream of the β-glucuronidase (GUS) reporter gene to identify the pattern of GUS water deficit stress-specific expression. Histochemical GUS assays showed in transgenic tobacco lines bearing the GUS gene driven by pObCVOMT and pObEOMT promoters, GUS was strongly expressed under water deficit stress. qRT-PCR analysis of pObCVOMT and pObEOMT transgenic plants confirmed the histochemical assays, indicating that the GUS expression is also significantly induced and up-regulated by increasing density of water deficit stress. This indicates these promoters are able to drive inducible expression. The cis-acting elements analysis showed that the pObCVOMT and pObEOMT promoters contained dehydration or water deficit-related transcriptional control elements.

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