scholarly journals PPARα Signaling is Activated by Cocoa in Mouse Liver

2013 ◽  
Vol 8 (5) ◽  
pp. 1934578X1300800
Author(s):  
Marco Fidaleo ◽  
Claudia Sartori
Keyword(s):  
Mouse Liver ◽  
Target Genes ◽  
Signal Modulation ◽  
Sod1 Gene ◽  
Serum Triglycerides ◽  
Oxidative Balance ◽  
Gene Level ◽  
Direct Binding ◽  
Somatic Index ◽  
Oxidation System

In this study we evaluated in mouse liver the effects of cocoa on PPARα signaling. To this aim, mouse diet was supplemented with 10%, w/w, cocoa for one and two weeks. We quantified the expression of PPARα target genes and PPARα gene level and some parameters related to PPARα activation (hepato-somatic index, peroxisomal β-oxidation system and catalase activity). Moreover, we evaluated antioxidant capacity of cocoa by detecting the expression of CAT and SOD1 genes (known to be involved in oxidative balance) and hypolipidemic properties on serum triglycerides. We made a parallel treatment with 0.025%, w/w, ciprofibrate, a well-known PPARα activator, to quantify signal modulation by cocoa. It is known that PPARα activation by ciprofibrate is mediated by direct binding to the receptor and strongly induces expression of target genes. Our results show that cocoa weakly up-regulates PPARα target genes as a consequence of the modulation of the PPARα gene level and does not improve the triglyceride profile in blood. Finally, cocoa increased SOD1 gene expression suggesting an antioxidant effect.

Analysis of Sterol-Regulatory Element-Binding Protein 1c Target Genes in Mouse Liver during Aging and High-Fat Diet

2013 ◽  
Vol 6 (2) ◽  
pp. 107-122 ◽  
Author(s):  
Frédéric Capel ◽  
Gaëlle Rolland-Valognes ◽  
Catherine Dacquet ◽  
Manuel Brun ◽  
Michel Lonchampt ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Mouse Liver ◽  
Target Genes ◽  
Binding Protein ◽  
Regulatory Element ◽  
High Fat ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

scholarly journals E1B-55-Kilodalton Protein Is Not Required To Block p53-Induced Transcription during Adenovirus Infection

2004 ◽  
Vol 78 (14) ◽  
pp. 7685-7697 ◽  
Author(s):  
Urs Hobom ◽  
Matthias Dobbelstein
Keyword(s):  
Virus Replication ◽  
Target Genes ◽  
Mutational Analysis ◽  
P300 Binding ◽  
Reporter Assays ◽  
Direct Binding ◽  
Infected Cells ◽  
Adenovirus E1b ◽  
Apoptosis Inhibitor ◽  
P53 Target Genes

ABSTRACT The adenovirus E1B-55-kDa protein binds and inactivates the tumor suppressor protein p53. However, the role of this interaction during infection is still poorly understood and was therefore examined here. Infection with a virus carrying the E1B-55-kDa mutation R239A, preventing the interaction with p53, led to the accumulation of p53. However, p53 target genes were not activated in the infected cells, although p53 phosphorylation did occur and the p53 antagonists Mdm2 and ΔNp73 did not accumulate. Deletion of E4orf6, alone or in combination with E1B-55-kDa, did not allow the induction of p53-responsive genes either. In transient reporter assays, the viral E1A-13S protein antagonized p53 activity; mutational analysis suggested that this depends partially on p300 binding, but it depends even more strongly on the interaction of E1A with the p400/TRRAP protein complex. However, viruses expressing E1A mutants lacking these binding activities, in combination with E1B-55-kDa R239A, still abolished p53 activity. In contrast, when the mutation of E1B-55-kDa at R239A was combined with a deletion of the apoptosis inhibitor E1B-19-kDa, infected cells showed more extensive apoptosis than after infection with single mutants, suggesting that accumulated p53, albeit transcriptionally inactive, might nonetheless enhance apoptosis. Despite extensive apoptosis of the infected cells, the deletion of E1B-19-kDa, in combination with the E1B-55-kDa mutation or in the presence of the constitutively active p53 mutant p53mt24-28, reduced virus replication less than fivefold. In conclusion, adenovirus does not need direct binding of E1B-55-kDa to inactivate p53, and forced p53 activity with consecutive apoptosis does not severely impair virus replication.

scholarly journals A Bayesian framework for inter-cellular information sharing improves dscRNA-seq quantification

2020 ◽  
Author(s):  
Avi Srivastava ◽  
Laraib Malik ◽  
Hirak Sarkar ◽  
Rob Patro
Keyword(s):  
Information Sharing ◽  
Target Genes ◽  
Expression Patterns ◽  
Sampling Bias ◽  
Bayesian Framework ◽  
Accurate Estimation ◽  
Multiple Modalities ◽  
Gene Level ◽  
Candidate Target ◽  
Empirical Priors

AbstractMotivationDroplet based single cell RNA-seq (dscRNA-seq) data is being generated at an unprecedented pace, and the accurate estimation of gene level abundances for each cell is a crucial first step in most dscRNA-seq analyses. When preprocessing the raw dscRNA-seq data to generate a count matrix, care must be taken to account for the potentially large number of multi-mapping locations per read. The sparsity of dscRNA-seq data, and the strong 3’ sampling bias, makes it difficult to disambiguate cases where there is no uniquely mapping read to any of the candidate target genes.ResultsWe introduce a Bayesian framework for information sharing across cells within a sample, or across multiple modalities of data using the same sample, to improve gene quantification estimates for dscRNA-seq data. We use an anchor-based approach to connect cells with similar gene expression patterns, and learn informative, empirical priors which we provide to alevin’s gene multi-mapping resolution algorithm. This improves the quantification estimates for genes with no uniquely mapping reads (i.e. when there is no unique intra-cellular information). We show our new model improves the per cell gene level estimates and provides a principled framework for information sharing across multiple modalities. We test our method on a combination of simulated and real datasets under various setups.AvailabilityThe information sharing model is included in alevin and is implemented in C++14. It is available as open-source software, under GPL v3, at https://github.com/COMBINE-lab/salmon as of version [email protected], [email protected]

scholarly journals Distinct and overlapping roles of ARID3A and ARID3B in regulating E2F‑dependent transcription via direct binding to E2F target genes

2021 ◽  
Vol 58 (4) ◽  
Author(s):  
Khandakar Saadat ◽  
Widya Lestari ◽  
Endrawan Pratama ◽  
Teng Ma ◽  
Sachiko Iseki ◽  
...  
Keyword(s):  
Target Genes ◽  
Direct Binding

scholarly journals A Bayesian framework for inter-cellular information sharing improves dscRNA-seq quantification

2020 ◽  
Vol 36 (Supplement_1) ◽  
pp. i292-i299
Author(s):  
Avi Srivastava ◽  
Laraib Malik ◽  
Hirak Sarkar ◽  
Rob Patro
Keyword(s):  
Information Sharing ◽  
Target Genes ◽  
Expression Patterns ◽  
Sampling Bias ◽  
Bayesian Framework ◽  
Accurate Estimation ◽  
Multiple Modalities ◽  
Gene Level ◽  
Candidate Target ◽  
Empirical Priors

Abstract Motivation Droplet-based single-cell RNA-seq (dscRNA-seq) data are being generated at an unprecedented pace, and the accurate estimation of gene-level abundances for each cell is a crucial first step in most dscRNA-seq analyses. When pre-processing the raw dscRNA-seq data to generate a count matrix, care must be taken to account for the potentially large number of multi-mapping locations per read. The sparsity of dscRNA-seq data, and the strong 3’ sampling bias, makes it difficult to disambiguate cases where there is no uniquely mapping read to any of the candidate target genes. Results We introduce a Bayesian framework for information sharing across cells within a sample, or across multiple modalities of data using the same sample, to improve gene quantification estimates for dscRNA-seq data. We use an anchor-based approach to connect cells with similar gene-expression patterns, and learn informative, empirical priors which we provide to alevin’s gene multi-mapping resolution algorithm. This improves the quantification estimates for genes with no uniquely mapping reads (i.e. when there is no unique intra-cellular information). We show our new model improves the per cell gene-level estimates and provides a principled framework for information sharing across multiple modalities. We test our method on a combination of simulated and real datasets under various setups. Availability and implementation The information sharing model is included in alevin and is implemented in C++14. It is available as open-source software, under GPL v3, at https://github.com/COMBINE-lab/salmon as of version 1.1.0.

c-Maf Induces Monocytic Differentiation and Apoptosis in Bipotent Myeloid Progenitors

Blood ◽  
1999 ◽  
Vol 94 (5) ◽  
pp. 1578-1589 ◽  
Author(s):  
Shrikanth P. Hegde ◽  
JingFeng Zhao ◽  
Richard A. Ashmun ◽  
Linda H. Shapiro
Keyword(s):  
Target Genes ◽  
Cell Model ◽  
Myeloid Cell ◽  
Model Systems ◽  
Monocytic Differentiation ◽  
Developmentally Regulated ◽  
Myeloid Progenitor ◽  
Myeloid Progenitor Cells ◽  
Direct Binding ◽  
Myeloid Progenitors

Abstract The transcriptional mechanisms that drive colony-forming unit granulocyte-macrophage (CFU-GM) myeloid progenitors to differentiate into cells of either the granulocytic or monocytic lineage are not fully understood. We have shown that the c-Maf and c-Myb transcription factors physically interact in myeloid cells to form inhibitory complexes that hinder transactivation of c-Myb target genes through direct binding to Myb consensus sites. These complexes arise in a developmentally regulated pattern, peaking at the promyelocyte stage, or in cell model systems, appearing soon after the induction of monocytic differentiation. We wished to determine if this developmentally related interaction is a consequence of myeloid differentiation or an intrinsic differentiating stimulus. Because the elevated Myb:Maf status seen in differentiating cells can be recapitulated by overexpression of c-Maf in myeloid cell lines, we inducibly expressed the c-Maf cDNA in 2 bipotent human myeloid progenitor cells. Elevated levels of c-Maf protein led to marked increases in Myb:Maf complexes and the accumulation of monocyte/macrophage cells, followed by eventual programmed cell death. Analysis of targets that could mediate these phenotypic changes indicated that c-Maf likely plays a key role in myeloid cell development through dual mechanisms; inhibition of a select set of c-Myb regulated targets, such as Bcl-2 and CD13/APN, coupled with the activation of as yet undefined differentiation-promoting genes.

scholarly journals Comparative Study of Regulation of RTA-Responsive Genes in Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8

2003 ◽  
Vol 77 (17) ◽  
pp. 9451-9462 ◽  
Author(s):  
Moon Jung Song ◽  
Hongyu Deng ◽  
Ren Sun
Keyword(s):  
Gene Expression ◽  
Life Cycle ◽  
Transcription Initiation ◽  
Target Genes ◽  
Human Herpesvirus ◽  
Lytic Replication ◽  
Human Herpesvirus 8 ◽  
Transcription Activator ◽  
Herpesvirus 8 ◽  
Direct Binding

ABSTRACT Replication and transcription activator (RTA) (also referred to as ORF50), an immediate-early gene product of Kaposi's sarcoma-associated herpesvirus (KSHV)/(human herpesvirus 8), plays a critical role in balancing the viral life cycle between latency and lytic replication. RTA has been shown to act as a strong transcription activator for several downstream genes of KSHV. Direct binding of RTA to DNA is thought to be one of the important mechanisms for transactivation of target genes, while indirect mechanisms are also implicated in RTA transactivation of certain selected genes. This study demonstrated direct binding of the DNA-binding domain of RTA (Rdbd) to a Kaposin (Kpsn) promoter sequence, which is highly homologous to the RTA-responsive element (RRE) of the PAN promoter. We undertook a comparative study of the RREs of PAN RNA, ORF57, vIL-6, and Kpsn to understand how RTA regulates gene expression during lytic replication. Comparing RNA abundance and transcription initiation rates of these RTA target genes in virus-infected cells suggested that the transcription initiation rate of the promoters is a major determinant of viral gene expression, rather than stability of the transcripts. RTA-mediated transactivation of reporters containing each RRE showed that their promoter strengths in a transient-transfection system were comparable to their transcription rates during reactivation. Moreover, our electrophoretic mobility shift assays of each RRE demonstrated that the highly purified Rdbd protein directly bound to the RREs. Based on these results, we conclude that direct binding of RTA to these target sequences contributes to their gene expression to various extents during the lytic life cycle of KSHV.

Transcriptional profiling reveals divergent roles of PPARα and PPARβ/δ in regulation of gene expression in mouse liver

2010 ◽  
Vol 41 (1) ◽  
pp. 42-52 ◽  
Author(s):  
Linda M. Sanderson ◽  
Mark V. Boekschoten ◽  
Beatrice Desvergne ◽  
Michael Müller ◽  
Sander Kersten
Keyword(s):  
Gene Expression ◽  
Mouse Liver ◽  
Target Genes ◽  
Glucose Utilization ◽  
Plasma Cholesterol ◽  
Transcriptional Profiling ◽  
Regulation Of Gene Expression ◽  
Lipoprotein Metabolism ◽  
Peroxisome Proliferator ◽  
Fed State

Little is known about the role of the transcription factor peroxisome proliferator-activated receptor (PPAR) β/δ in liver. Here we set out to better elucidate the function of PPARβ/δ in liver by comparing the effect of PPARα and PPARβ/δ deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARα and PPARβ/δ deletion was similar, whereas in fasted state the effect of PPARα deletion was much more pronounced, consistent with the pattern of gene expression of PPARα and PPARβ/δ. Minor overlap was found between PPARα- and PPARβ/δ-dependent gene regulation in liver. Pathways upregulated by PPARβ/δ deletion were connected to innate immunity and inflammation. Pathways downregulated by PPARβ/δ deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPARβ/δ−/− mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPARβ/δ target genes. In contrast to PPARα−/− mice, no changes in plasma free fatty acid, plasma β-hydroxybutyrate, liver triglycerides, and liver glycogen were observed in PPARβ/δ−/− mice. Our data indicate that PPARβ/δ governs glucose utilization and lipoprotein metabolism and has an important anti-inflammatory role in liver. Overall, our analysis reveals divergent roles of PPARα and PPARβ/δ in regulation of gene expression in mouse liver.

The COUP-TFII variant lacking a DNA-binding domain inhibits the activation of the Cyp7a1 promoter through physical interaction with COUP-TFII

2013 ◽  
Vol 452 (2) ◽  
pp. 345-357 ◽  
Author(s):  
Tomoko Yamazaki ◽  
Jun-ichi Suehiro ◽  
Hideki Miyazaki ◽  
Takashi Minami ◽  
Tatsuhiki Kodama ◽  
...  
Keyword(s):  
Dna Binding ◽  
Transcriptional Control ◽  
Target Genes ◽  
Binding Domain ◽  
Physical Interaction ◽  
Dna Binding Domain ◽  
Factor Ii ◽  
Huh7 Cells ◽  
Direct Binding ◽  
Cytochrome P450 Family

The COUP-TFII (chicken ovalbumin upstream promoter-transcription factor II) nuclear receptor, which is composed of a DNA-binding domain and a ligand-binding domain, exerts pleiotropic effects on development and cell differentiation by regulating the transcription of its target genes, including Cyp7a1 (cytochrome P450, family 7, subfamily a, polypeptide 1), which plays important roles in catabolism of cholesterol in the liver. Although multiple variants of COUP-TFII exist, their roles in the regulation of Cyp7a1 expression have not been elucidated. In the present study, we investigated the roles of COUP-TFII-V2 (variant 2), which lacks a DNA-binding domain, in the regulation of the transcriptional control of the Cyp7a1 gene by COUP-TFII in hepatocellular carcinoma cells. We found that COUP-TFII-V2 was significantly expressed in Huh7 cells, in which Cyp7a1 was not expressed. Furthermore, knockdown of COUP-TFII-V2 enhanced endogenous Cyp7a1 expression in Huh7 cells. Although COUP-TFII activates the Cyp7a1 promoter through direct binding to DNA, this activation was affected by COUP-TFII-V2, which physically interacted with COUP-TFII and inhibited its DNA-binding ability. Chromatin immunoprecipitation assays showed that COUP-TFII-V2 inhibited the binding of endogenous COUP-TFII to the intact Cyp7a1 promoter. The results of the present study suggest that COUP-TFII-V2 negatively regulates the function of COUP-TFII by inhibiting its binding to DNA to decrease Cyp7a1 expression.

Sign in / Sign up

Export Citation Format

Share Document