Regulation of TGF‐β1‐inducible angiotensinogen gene transcription in lung cells by core promoter SNPs (834.6)

Tetrandrine (Tet) (C38H42O8N2; molecular weight, 622), an alkaloid isolated from the Chinese medicinal herb Stephania tetrandra, has been shown to elicit anti-inflammatory and anti-fibrotic effects in pulmonary diseases, but the mechanism of action has yet to be investigated. In this study, we tested whether Tet exerts anti-fibrotic effects on rat hepatic fibrosis through anti-NFκB pathways. After bile-duct ligation, rats were given Tet (1 or 5 mg/kg) or silymarin (50 mg/kg, as a positive control) by gavage twice daily for 3 weeks. Liver sections were taken for Sirius red quantitative scoring, immunofluorescence double staining of α-smooth muscle actin (α-SMA) and NFκB, and for quantitative determinations of the mRNA expression levels of TGF-β1, α-SMA, collagen 1α2, inducible nitric oxide synthase (iNOS), intercellular adhesion molecule 1 (ICAM-1), metallothionein, vascular endothelial growth factor (VEGF), and VEGF type II receptor (VEGFR2) genes. The results showed that both Tet and silymarin treatment significantly reduced the fibrosis scores and hepatic collagen content of BDL rats, compared with no treatment. Both Tet and silymarin treatments decreased the number of α-SMA- and NFκB-positive cells in fibrotic livers. Moreover, Tet and silymarin treatments attenuated the mRNA expression levels of TGF-β1,α-SMA, collagen 1α2, iNOS, ICAM-1, VEGF, and VEGFR2 genes, and induced the mRNA expression of the metallothionein gene. This study suggests that the anti-fibrotic effects of Tet were related to the reduction of fibrosis-related gene transcription, the attenuation of NFκB-activated pathways, and the induction of metallothionein gene transcription in the livers of BDL rats.

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Repression of the Luteinizing Hormone Receptor Gene Promoter by Cross Talk among EAR3/COUP-TFI, Sp1/Sp3, and TFIIB

Molecular and Cellular Biology ◽

10.1128/mcb.23.19.6958-6972.2003 ◽

2003 ◽

Vol 23 (19) ◽

pp. 6958-6972 ◽

Cited By ~ 33

Author(s):

Ying Zhang ◽

Maria L. Dufau

Keyword(s):

Luteinizing Hormone ◽

Gene Transcription ◽

Cross Talk ◽

Hormone Receptor ◽

Core Promoter ◽

Adaptor Protein ◽

Inhibitory Effect ◽

Luteinizing Hormone Receptor ◽

Orphan Receptors ◽

Basal Transcription

ABSTRACT Transcription of luteinizing hormone receptor (LHR) gene is activated by Sp1/Sp3 at two Sp1 sites and is repressed by nuclear orphan receptors EAR2 and EAR3 through a direct-repeat (DR) motif. To elucidate the mechanism of the orphan receptor-mediated gene repression, we explored the functional connection between the orphan receptors and Sp1/Sp3 complex, and its impact on the basal transcription machinery. The Sp1(I) site was identified as critical for the repression since its mutation reduced the inhibition by EAR2 and abolished the inhibition by EAR3. Cotransfection analyses in SL2 cells showed that both Sp1 and Sp3 were required for this process since EAR3 displayed a complete Sp1/Sp3-dependent inhibitory effect. Functional cooperation between Sp1 and DR domains was further supported by mutual recruitment of EAR3 and Sp1/Sp3 bound to their cognate sites. Deletion of EAR3 N-terminal and DNA-binding domains that reduced its interaction with Sp1 impaired its inhibitory effect on human LHR (hLHR) gene transcription. Furthermore, we demonstrate interaction of TFIIB with Sp1/Sp3 at the Sp1(I) site besides its association with EAR3 and the TATA-less core promoter region. Such interaction relied on Sp1 site-bound Sp1/Sp3 complex and adaptor protein(s) present in the JAR nuclear extracts. We further demonstrated that EAR3 specifically decreased association of TFIIB to the Sp1(I) site without interfering on its interaction with the hLHR core promoter. The C-terminal region of EAR3, which did not participate in its interaction with Sp1, was required for its inhibitory function and may affect the association of TFIIB with Sp1. Moreover, perturbation of the association of TFIIB with Sp1 by EAR3 was reflected in the reduced recruitment of RNA polymerase II to the promoter. Overexpression of TFIIB counteracted the inhibitory effect of EAR3 and activated hLHR gene transcription in an Sp1 site-dependent manner. These findings therefore indicate that TFIIB is a key component in the regulatory control of EAR3 and Sp1/Sp3 on the initiation complex. Such cross talk among EAR3, TFIIB, and Sp1/Sp3 reveals repression of hLHR gene transcription by nuclear orphan receptors is achieved via perturbation of communication between Sp1/Sp3 at the Sp1-1 site and the basal transcription initiator complex.

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Angiotensinogen Gene Core Promoter Variants and Non-Modulating Hypertension

Hypertension ◽

10.1161/hy1201.096545 ◽

2001 ◽

Vol 38 (6) ◽

pp. 1250-1254 ◽

Cited By ~ 11

Author(s):

Karl F. Hilgers ◽

Christian Delles ◽

Roland Veelken ◽

Roland E. Schmieder

Keyword(s):

Core Promoter ◽

Angiotensinogen Gene

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TTF-1, a Homeodomain-containing Transcription Factor, Participates in the Control of Body Fluid Homeostasis by Regulating Angiotensinogen Gene Transcription in the Rat Subfornical Organ

Journal of Biological Chemistry ◽

10.1074/jbc.m303157200 ◽

2003 ◽

Vol 278 (29) ◽

pp. 27043-27052 ◽

Cited By ~ 21

Author(s):

Young June Son ◽

Min Kyu Hur ◽

Byung Jun Ryu ◽

Sang Kyu Park ◽

Giuseppe Damante ◽

...

Keyword(s):

Transcription Factor ◽

Gene Transcription ◽

Body Fluid ◽

Subfornical Organ ◽

Fluid Homeostasis ◽

Angiotensinogen Gene ◽

Body Fluid Homeostasis

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Protein Kinase C δ Induces Transcription of the TP53 Tumor Suppressor Gene by Controlling Death-Promoting Factor Btf in the Apoptotic Response to DNA Damage

Molecular and Cellular Biology ◽

10.1128/mcb.01126-07 ◽

2007 ◽

Vol 27 (24) ◽

pp. 8480-8491 ◽

Cited By ~ 62

Author(s):

Hanshao Liu ◽

Zheng-Guang Lu ◽

Yoshio Miki ◽

Kiyotsugu Yoshida

Keyword(s):

Dna Damage ◽

Protein Kinase C ◽

Protein Kinase ◽

Tumor Suppressor ◽

Gene Transcription ◽

Core Promoter ◽

Genotoxic Stress ◽

Tp53 Gene ◽

Transcriptional Level ◽

Kinase C

ABSTRACT Expression of the TP53 tumor suppressor is tightly controlled for its ability to function as a critical regulator of cell growth, proliferation, and death in response to DNA damage. However, little is known about the mechanisms and contributions of the transcriptional regulation of TP53. Here we report that protein kinase C δ (PKCδ), a ubiquitously expressed member of the novel subfamily of PKC isoforms, transactivates TP53 expression at the transcriptional level. Reporter assays demonstrated that PKCδ induces the promoter activity of TP53 through the TP53 core promoter element (CPE-TP53) and that such induction is enhanced in response to DNA damage. The results also demonstrate that, upon exposure to genotoxic stress, PKCδ activates and interacts with the death-promoting transcription factor Btf to co-occupy CPE-TP53. Inhibition of PKCδ activity decreases the affinity of Btf for CPE-TP53, thereby reducing TP53 expression at both the mRNA and the protein levels. In concert with these results, we show that disruption of Btf-mediated TP53 gene transcription by RNA interference leads to suppression of TP53-mediated apoptosis following genotoxic stress. These findings provide evidence that activation of TP53 gene transcription by PKCδ triggers TP53-dependent apoptosis in response to DNA damage.

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Polymorphism of 5’upstream core promoter region of angiotensinogen gene (A-20C) and proteinuria in children with IgA nephropathy

Nephrology ◽

10.1111/j.1440-1797.2002.tb00538.x ◽

2008 ◽

Vol 7 ◽

pp. A98-A98

Author(s):

K NAKANISHI ◽

M SAKO ◽

K IIJIMA ◽

N YOSHIKAWA

Keyword(s):

Iga Nephropathy ◽

Promoter Region ◽

Core Promoter ◽

Core Promoter Region ◽

Angiotensinogen Gene

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Core promoter factor TAF9B regulates neuronal gene expression

eLife ◽

10.7554/elife.02559 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 17

Author(s):

Francisco J Herrera ◽

Teppei Yamaguchi ◽

Henk Roelink ◽

Robert Tjian

Keyword(s):

Gene Expression ◽

Motor Neuron ◽

Gene Transcription ◽

Core Promoter ◽

Es Cells ◽

Specific Gene ◽

Neuron Differentiation ◽

Neuronal Gene ◽

Promoter Recognition ◽

Neuronal Genes

Emerging evidence points to an unexpected diversification of core promoter recognition complexes that serve as important regulators of cell-type specific gene transcription. Here, we report that the orphan TBP-associated factor TAF9B is selectively up-regulated upon in vitro motor neuron differentiation, and is required for the transcriptional induction of specific neuronal genes, while dispensable for global gene expression in murine ES cells. TAF9B binds to both promoters and distal enhancers of neuronal genes, partially co-localizing at binding sites of OLIG2, a key activator of motor neuron differentiation. Surprisingly, in this neuronal context TAF9B becomes preferentially associated with PCAF rather than the canonical TFIID complex. Analysis of dissected spinal column from Taf9b KO mice confirmed that TAF9B also regulates neuronal gene transcription in vivo. Our findings suggest that alternative core promoter complexes may provide a key mechanism to lock in and maintain specific transcriptional programs in terminally differentiated cell types.

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