scholarly journals Bradykinin B2 receptor null mice harboring a Ser23-to-Ala substitution in the p53 gene are protected from renal dysgenesis

2008 ◽  
Vol 295 (5) ◽  
pp. F1404-F1413 ◽  
Author(s):  
Samir S. El-Dahr ◽  
Karam Aboudehen ◽  
Susana Dipp
Keyword(s):  
Transcriptional Activation ◽  
Expression Patterns ◽  
Terminal Differentiation ◽  
P53 Gene ◽  
Intermediate Phenotype ◽  
Rt Pcr ◽  
Nephron Progenitors ◽  
Normal Expression ◽  
Functional Relevance ◽  
Renal Organogenesis

A physiological cross talk operates between the tumor suppressor protein p53 and the bradykinin B2 receptor ( BdkrB2) during renal organogenesis. Thus, although BdkrB2 is a target for p53-mediated transcriptional activation, BdkrB2 is required to restrict p53 proapoptotic activity. We previously demonstrated that BdkrB2−/− embryos exposed to gestational salt stress develop renal dysgenesis as a result of p53-mediated apoptosis of nephron progenitors and repression of the terminal differentiation program. Compared with wild-type kidneys, BdkrB2−/− express abnormally high levels of the Checkpoint kinase (Chk1), which activates p53 via Ser23 phosphorylation. To define the functional relevance of p53S23 phosphorylation, we generated a compound strain of BdkrB2−/− mice harboring a homozygous Ser23-to-Ala (S23A) mutation in the p53 gene by crossing BdkrB2−/− with p53S23A knockin mice. Unlike salt-stressed BdkrB2−/− pups, which exhibit renal dysgenesis, homozygous S23A;BdkrB2−/− littermates are protected and have normal renal development. Heterozygous S23A;BdkrB2−/− mice have an intermediate phenotype. The p53-S23A substitution was associated with amelioration of apoptosis and restored markers of nephrogenesis and tubulogenesis. Real-time quantitative RT-PCR of terminal differentiation genes demonstrated that the S23A substitution restored normal expression patterns of aquaporin-2, Na-Cl cotransporter, Na-K-2Cl cotransporter, Na-bicarbonate cotransporter, and Sglt1. We conclude that p53 phosphorylation on Ser23 is an essential step in the signaling pathway mediating the susceptibility of BdkrB2−/− mutants to renal dysgenesis.

scholarly journals The potential regulatory role of hsa_circ_0004104 in the persistency of atrial fibrillation by promoting cardiac fibrosis via TGF-β pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yuanfeng Gao ◽  
Ye Liu ◽  
Yuan Fu ◽  
Qianhui Wang ◽  
Zheng Liu ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Expression Patterns ◽  
In Silico Analysis ◽  
Significant Negative Correlation ◽  
Circular Rnas ◽  
Tgf Beta ◽  
Rt Pcr ◽  
Derivation Cohort ◽  
Tgf Β1

Abstract Introduction The progression of paroxysmal AF (PAF) to persistent AF (PsAF) worsens the prognosis of AF, but its underlying mechanisms remain elusive. Recently, circular RNAs (circRNAs) were reported to be associated with cardiac fibrosis. In case of the vital role of cardiac fibrosis in AF persistency, we hypothesis that circRNAs may be potential regulators in the process of AF progression. Materials and methods 6 persistent and 6 paroxysmal AF patients were enrolled as derivation cohort. Plasma circRNAs expressions were determined by microarray and validated by RT-PCR. Fibrosis level, manifested by serum TGF-β, was determined by ELISA. Pathways and related non-coding RNAs involving in the progression of AF regulated were predicted by in silico analysis. Results PsAF patients showed a distinct circRNAs expression profile with 92 circRNAs significantly dysregulated (fold change ≥ 2, p < 0.05), compared with PAF patients. The validity of the expression patterns was subsequently validated by RT-PCR in another 60 AF patients (30 PsAF and PAF, respectively). In addition, all the 5 up and down regulated circRNAs were clustered in MAPK and TGF-beta signaling pathway by KEGG pathway analysis. Among the 5 circRNAs, hsa_circ_0004104 was consistently downregulated in PsAF group (0.6 ± 0.33 vs 1.46 ± 0.41, p < 0.001) and predicted to target several AF and/or cardiac fibrosis related miRNAs reported by previous studies. In addition, TGF-β1 level was significantly higher in the PsAF group (5560.23 ± 1833.64 vs 2236.66 ± 914.89, p < 0.001), and hsa_circ_0004104 showed a significant negative correlation with TGF-β1 level (r = − 0.797, p < 0.001). Conclusion CircRNAs dysregulation plays vital roles in AF persistency. hsa_circ_0004104 could be a potential regulator and biomarker in AF persistency by promoting cardiac fibrosis via targeting MAPK and TGF-beta pathways.

scholarly journals Transcriptome-Based Identification and Molecular Evolution of the Cytochrome P450 Genes and Expression Profiling under Dimethoate Treatment in Amur Stickleback (Pungitius sinensis)

Animals ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 873 ◽  
Author(s):  
Jun Cao ◽  
Xiuzhu Cheng
Keyword(s):  
Expression Profiling ◽  
Transcriptome Sequencing ◽  
Cell Metabolism ◽  
Functional Divergence ◽  
Expression Patterns ◽  
Cytochrome P450s ◽  
Cytochrome P450 Genes ◽  
Membrane Bound ◽  
Functional Relevance ◽  
Functional Investigation

Cytochrome P450s (CYPs) are a family of membrane-bound mono-oxygenase proteins, which are involved in cell metabolism and detoxification of various xenobiotic substances. In this study, we identified 58 putative CYP genes in Amur stickleback (Pungitius sinensis) based on the transcriptome sequencing. Conserved motif distribution suggested their functional relevance within each group. Some present recombination events have accelerated the evolution of this gene family. Moreover, a few positive selection sites were identified, which may have accelerated the functional divergence of this family of proteins. Expression patterns of these CYP genes were investigated and indicated that most were affected by dimethoate treatment, suggesting that CYPs were involved in the detoxication of dimethoate. This study will provide a foundation for the further functional investigation of CYP genes in fishes.

scholarly journals Dnmt1 Expression in Pre- and Postimplantation Embryogenesis and the Maintenance of IAP Silencing

2004 ◽  
Vol 24 (4) ◽  
pp. 1640-1648 ◽  
Author(s):  
F. Gaudet ◽  
W. M. Rideout ◽  
A. Meissner ◽  
J. Dausman ◽  
H. Leonhardt ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Dna Methyltransferase ◽  
Coat Color ◽  
Expression Patterns ◽  
Methylation Status ◽  
Dna Methyltransferase 1 ◽  
Type Particle ◽  
Methylation Patterns ◽  
Dnmt1 Expression ◽  
Affect Gene Expression

ABSTRACT The methylation of intracisternal A-type particle (IAP) sequences is maintained during mouse embryogenesis. Methylation suppresses IAP expression and the potential for mutagenesis by retrotransposition, but it is not clear how methylation of these elements is maintained during the embryonic stages when the bulk of the genome is being demethylated. It has been suggested that the high levels of DNA methyltransferase-1 (Dnmt1) present during cleavage could be important for keeping IAPs methylated. To test this hypothesis, we combined mutant alleles of Dnmt1 with an agouti allele (Aiapy ), which provided a coat color readout for the methylation status of the IAP insertion in the agouti locus. We found that reduction in Dnmt1 levels directly impacted methylation at this locus, leading to stable transcriptional activation of the agouti gene in the adult. Specifically, the short maternal Dnmt1 protein was important in maintaining methylation at the Aiapy locus in cleavage embryos, whereas the longer Dnmt1 isoform found in somatic cells was important in maintaining IAP methylation during the postimplantation stage. These results underscore the importance of maintaining proper maintenance of methylation patterns during gestation and suggest that interference with this process may stably affect gene expression patterns in the adult and may have profound phenotypic consequences.

scholarly journals Differential regulation of gastrulation and neuroectodermal gene expression by Snail in the Drosophila embryo

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3683-3691 ◽  
Author(s):  
K. Hemavathy ◽  
X. Meng ◽  
Y.T. Ip
Keyword(s):  
Cell Fate ◽  
Target Genes ◽  
Expression Patterns ◽  
Cell Movement ◽  
Drosophila Embryo ◽  
Intermediate Phenotype ◽  
Gene Products ◽  
Mesodermal Cell ◽  
Possible Cause ◽  
Mesodermal Lineage

The initiation of mesoderm differentiation in the Drosophila embryo requires the gene products of twist and snail. In either mutant, the ventral cell invagination during gastrulation is blocked and no mesoderm-derived tissue is formed. One of the functions of Snail is to repress neuroectodermal genes and restrict their expressions to the lateral regions. The derepression of the neuroectodermal genes into the ventral region in snail mutant is a possible cause of defects in gastrulation and in mesoderm differentiation. To investigate such possibility, we analysed a series of snail mutant alleles. We found that different neuroectodermal genes respond differently in various snail mutant background. Due to the differential response of target genes, one of the mutant alleles, V2, that has reduced Snail function showed an intermediate phenotype. In V2 embryos, neuroectodermal genes, such as single-minded and rhomboid, are derepressed while ventral invagination proceeds normally. However, the differentiation of these invaginated cells into mesodermal lineage is disrupted. The results suggest that the establishment of mesodermal cell fate requires the proper restriction of neuroectodermal genes, while the ventral cell movement is independent of the expression patterns of these genes. Together with the data showing that the expression of some ventral genes disappear in snail mutants, we propose that Snail may repress or activate another set of target genes that are required specifically for gastrulation.

scholarly journals Key Regulatory Pathways, MicroRNAs, and Target Genes Participate in Adventitious Root Formation of Acer Rubrum L

2021 ◽  
Author(s):  
Wenpeng Zhu ◽  
Manyu Zhang ◽  
Jianyi Li ◽  
Hewen Zhao ◽  
Kezhong Zhang ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Seedling Survival ◽  
Expression Patterns ◽  
Economic Value ◽  
Acer Rubrum ◽  
Pcr Analysis ◽  
Asexual Propagation ◽  
Regulatory Pathways

Abstract BackgroundAcer rubrum L. is a colorful ornamental tree with great economic value. Because this tree is difficult to root under natural conditions and the seedling survival rate is low, vegetative propagation methods are often used. Because the formation of adventitious roots (ARs) is essential for the survival of asexual propagation of A. rubrum, it is necessary to investigate the molecular regulatory mechanisms in the formation of ARs of A. ruburm. To address this knowledge gap, we sequenced the transcriptome and sRNA of the A. rubrum variety ‘Autumn Fantasy’ using high-throughput sequencing and explored changes in gene and microRNA (miRNA) expression in response to exogenous auxin treatment. ResultsWe identified 82,468 differentially expressed genes between the treated and untreated ARs, as well as 48 known and 95 novel miRNAs. We also identified 172 target genes of the known miRNAs using degradome sequencing. Two regulatory pathways (ubiquitin mediated proteolysis and plant hormone signal transduction), Ar-miR160a and the target gene ArARF10 were shown to be involved in the auxin response. We further investigated the expression patterns and regulatory roles of ArARF10 through subcellular localization, transcriptional activation, plant transformation, qRT-PCR analysis, and GUS staining. ConclusionsDifferential expression patterns indicated the Ar-miR160a-ArARF10 interaction might play a significant role in the regulation of AR formation in A. rubrum. Our study provided new insights into mechanisms underlying the regulation of AR formation in A. rubrum.

scholarly journals Development of cDNA normalization system and preliminary transcription analysis of KCS genes in apple tissues

2011 ◽  
Vol 59 (3) ◽  
pp. 9-12 ◽  
Author(s):  
Zsolt Albert ◽  
Cs. Deák ◽  
A. Miskó ◽  
M. Tóth ◽  
I. Papp
Keyword(s):  
Gene Expression ◽  
Expression System ◽  
Expression Patterns ◽  
Housekeeping Genes ◽  
Apple Fruit ◽  
Rt Pcr ◽  
Specific Primers ◽  
Specific Expression ◽  
Transcription Analysis ◽  
Tissue Specific

Wax production is an important aspect of apple (Malus domestica Borkh.) fruit development from both theoretical and practical point of views. The complex molecular mechanism that controls wax biosynthesis is still widely unknown but many studies focused on this topic. We aimed to develop further the experimental framework of these efforts with a description of an improved reference genes expression system. Results in the literature show that similarities exist among the expression of some housekeeping genes of different plant species. Based on these considerations and on gene expression data from Arabidopsis thaliana, some genes in apple were assigned for analysis. EST sequences of apple were used to design specific primers for RT-PCR experiments. Isolation of intact RNA from different apple tissues and performing RT-PCR reaction were also key point in obtaining expression patterns. To monitor DNA contamination of the RNA samples, specific primers were used that amplify intron-containing sequences from the cDNA. We found that actin primers can be used for the detection of intron containing genomic DNA, and tubulin primers are good internal controls in RT-PCR experiments. We were able to make a difference between tissue-specific and tissue-independent gene-expression, furthermore we found tissue specific differences between the expression patterns of candidate genes, that are potentially involved in wax-biosynthesis. Our results show that KCS1 and KCS4 are overexpressed in the skin tissue, this could mean that these genes have skin-specific expression in apple fruit.

Expression and intracellular localization of Nanos2-homologue protein in primordial germ cells and spermatogonial stem cells

Zygote ◽  
2019 ◽  
Vol 27 (02) ◽  
pp. 82-88 ◽  
Author(s):  
Vivek Pandey ◽  
Anima Tripathi ◽  
Pawan K. Dubey
Keyword(s):  
Stem Cells ◽  
Flow Cytometry ◽  
Germ Cells ◽  
Expression Patterns ◽  
Intracellular Localization ◽  
Primordial Germ Cells ◽  
Type A ◽  
Spermatogonial Stem Cells ◽  
Single Type ◽  
Rt Pcr

SummaryThe decision by germ cells to differentiate and undergo either oogenesis or spermatogenesis takes place during embryonic development and Nanos plays an important role in this process. The present study was designed to investigate the expression patterns in rat of Nanos2-homologue protein in primordial germ cells (PGCs) over different embryonic developmental days as well as in spermatogonial stem cells (SSCs). Embryos from three different embryonic days (E8.5, E10.5, E11.5) and SSCs were isolated and used to detect Nanos2-homologue protein using immunocytochemistry, western blotting, reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry. Interestingly, Nanos2 expression was detected in PGCs at day E11.5 onwards and up to colonization of PGCs in the genital ridge of fetal gonads. No Nanos2 expression was found in PGCs during early embryonic days (E8.5 and 10.5). Furthermore, immunohistochemical and immunofluorescence data revealed that Nanos2 expression was restricted within a subpopulation of undifferentiated spermatogonia (As, single type A SSCs and Apr, paired type A SSCs). The same results were confirmed by our western blot and RT-PCR data, as Nanos2 protein and transcripts were detected only in PGCs from day E11.5 and in undifferentiated spermatogonia (As and Apr). Furthermore, Nanos2-positive cells were also immunodetected and sorted using flow cytometry from the THY1-positive SSCs population, and this strengthened the idea that these cells are stem cells. Our findings suggested that stage-specific expression of Nanos2 occurred on different embryonic developmental days, while during the postnatal period Nanos2 expression is restricted to As and Apr SSCs.

scholarly journals Characteristics and Expression Pattern of MYC Genes in Triticum aestivum, Oryza sativa, and Brachypodium distachyon

Plants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 274 ◽  
Author(s):  
Shoukun Chen ◽  
Hongyan Zhao ◽  
Tengli Luo ◽  
Yue Liu ◽  
Xiaojun Nie ◽  
...  
Keyword(s):  
Transcriptional Activation ◽  
Leucine Zipper ◽  
Brachypodium Distachyon ◽  
Expression Patterns ◽  
Terminal Region ◽  
Gene Promoters ◽  
Interaction Domain ◽  
Specific Expression ◽  
Systematic Analysis ◽  
Transcriptional Activation Domain

Myelocytomatosis oncogenes (MYC) transcription factors (TFs) belong to basic helix-loop-helix (bHLH) TF family and have a special bHLH_MYC_N domain in the N-terminal region. Presently, there is no detailed and systematic analysis of MYC TFs in wheat, rice, and Brachypodium distachyon. In this study, 26 TaMYC, 7 OsMYC, and 7 BdMYC TFs were identified and their features were characterized. Firstly, they contain a JAZ interaction domain (JID) and a putative transcriptional activation domain (TAD) in the bHLH_MYC_N region and a BhlH region in the C-terminal region. In some cases, the bHLH region is followed by a leucine zipper region; secondly, they display tissue-specific expression patterns: wheat MYC genes are mainly expressed in leaves, rice MYC genes are highly expressed in stems, and B. distachyon MYC genes are mainly expressed in inflorescences. In addition, three types of cis-elements, including plant development/growth-related, hormone-related, and abiotic stresses-related were identified in different MYC gene promoters. In combination with the previous studies, these results indicate that MYC TFs mainly function in growth and development, as well as in response to stresses. This study laid a foundation for the further functional elucidation of MYC genes.

scholarly journals An animal model study on the gene expression profile of meniscal degeneration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yehan Fang ◽  
Hui Huang ◽  
Gang Zhou ◽  
Qinghua Wang ◽  
Feng Gao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pathway Analysis ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Control Group ◽  
Ion Binding ◽  
Endoplasmic Reticulum Membrane ◽  
Rt Pcr ◽  
Go Analysis ◽  
Meniscal Degeneration

AbstractMeniscal degeneration is a very common condition in elderly individuals, but the underlying mechanisms of its occurrence are not completely clear. This study examines the molecular mechanisms of meniscal degeneration. The anterior cruciate ligament (ACL) and lateral collateral ligament (LCL) of the right rear limbs of seven Wuzhishan mini-pigs were resected (meniscal degeneration group), and the left rear legs were sham-operated (control group). After 6 months, samples were taken for gene chip analysis, including differentially expressed gene (DEG) analysis, gene ontology (GO) analysis, clustering analysis, and pathway analysis. The selected 12 DEGs were validated by real time reverse transcription-polymerase chain reaction (RT-PCR). The two groups showed specific and highly clustered DEGs. A total of 893 DEGs were found, in which 537 are upregulated, and 356 are downregulated. The GO analysis showed that the significantly affected biological processes include nitric oxide metabolic process, male sex differentiation, and mesenchymal morphogenesis, the significantly affected cellular components include the endoplasmic reticulum membrane, and the significantly affected molecular functions include transition metal ion binding and iron ion binding. The pathway analysis showed that the significantly affected pathways include type II diabetes mellitus, inflammatory mediator regulation of TRP channels, and AMPK signaling pathway. The results of RT-PCR indicate that the microarray data accurately reflects the gene expression patterns. These findings indicate that several molecular mechanisms are involved in the development of meniscal degeneration, thus improving our understanding of meniscal degeneration and provide molecular therapeutic targets in the future.

scholarly journals Distinct p53 acetylation cassettes differentially influence gene-expression patterns and cell fate

2006 ◽  
Vol 173 (4) ◽  
pp. 533-544 ◽  
Author(s):  
Chad D. Knights ◽  
Jason Catania ◽  
Simone Di Giovanni ◽  
Selen Muratoglu ◽  
Ricardo Perez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Protein Interactions ◽  
Posttranslational Modifications ◽  
Biological Activities ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
P53 Gene ◽  
Protein Protein Interactions

The activity of the p53 gene product is regulated by a plethora of posttranslational modifications. An open question is whether such posttranslational changes act redundantly or dependently upon one another. We show that a functional interference between specific acetylated and phosphorylated residues of p53 influences cell fate. Acetylation of lysine 320 (K320) prevents phosphorylation of crucial serines in the NH2-terminal region of p53; only allows activation of genes containing high-affinity p53 binding sites, such as p21/WAF; and promotes cell survival after DNA damage. In contrast, acetylation of K373 leads to hyperphosphorylation of p53 NH2-terminal residues and enhances the interaction with promoters for which p53 possesses low DNA binding affinity, such as those contained in proapoptotic genes, leading to cell death. Further, acetylation of each of these two lysine clusters differentially regulates the interaction of p53 with coactivators and corepressors and produces distinct gene-expression profiles. By analogy with the “histone code” hypothesis, we propose that the multiple biological activities of p53 are orchestrated and deciphered by different “p53 cassettes,” each containing combination patterns of posttranslational modifications and protein–protein interactions.

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