scholarly journals Sequences downstream of the bHLH domain of the Xenopus hairy-related transcription factor-1 act as an extended dimerization domain that contributes to the selection of the partners

2004 ◽  
Vol 276 (1) ◽  
pp. 47-63 ◽  
Author(s):  
Vincent Taelman ◽  
Réginald Van Wayenbergh ◽  
Marion Sölter ◽  
Bruno Pichon ◽  
Tomas Pieler ◽  
...  
Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1277 ◽  
Author(s):  
Kaur ◽  
Rawal ◽  
Siddiqui ◽  
Rohilla ◽  
Sharma ◽  
...  

Given the important role of angiogenesis in liver pathology, the current study investigated the role of Runt-related transcription factor 1 (RUNX1), a regulator of developmental angiogenesis, in the pathogenesis of non-alcoholic steatohepatitis (NASH). Quantitative RT-PCRs and a transcription factor analysis of angiogenesis-associated differentially expressed genes in liver tissues of healthy controls, patients with steatosis and NASH, indicated a potential role of RUNX1 in NASH. The gene expression of RUNX1 was correlated with histopathological attributes of patients. The protein expression of RUNX1 in liver was studied by immunohistochemistry. To explore the underlying mechanisms, in vitro studies using RUNX1 siRNA and overexpression plasmids were performed in endothelial cells (ECs). RUNX1 expression was significantly correlated with inflammation, fibrosis and NASH activity score in NASH patients. Its expression was conspicuous in liver non-parenchymal cells. In vitro, factors from steatotic hepatocytes and/or VEGF or TGF- significantly induced the expression of RUNX1 in ECs. RUNX1 regulated the expression of angiogenic and adhesion molecules in ECs, including CCL2, PECAM1 and VCAM1, which was shown by silencing or over-expression of RUNX1. Furthermore, RUNX1 increased the angiogenic activity of ECs. This study reports that steatosis-induced RUNX1 augmented the expression of adhesion and angiogenic molecules and properties in ECs and may be involved in enhancing inflammation and disease severity in NASH.


2007 ◽  
Vol 194 (1) ◽  
pp. 223-241 ◽  
Author(s):  
Zhihao Liu ◽  
Fengrui Wu ◽  
Baowei Jiao ◽  
Xiuyue Zhang ◽  
Chongjiang Hu ◽  
...  

To address the roles of doublesex and mab-3-related transcription factor 1 (Dmrt1), forkhead transcription factor gene 2 (Foxl2), and aromatase in sex differentiation of Southern catfish, the cDNA sequences of these genes were isolated from the gonads. Dmrt1a and Dmrt1b were found to be expressed in the gonads, being higher in the testis. A low expression level of Dmrt1b was also detected in the intestine and kidney of the male. Foxl2 was found to be expressed extensively in the brain (B), pituitary (P), gill and gonads (G), with the highest level in the ovary, indicating the possible involvement of Foxl2 in the B–P–G axis. Cytochrome P450 (Cyp)19b was found to be expressed in the brain, spleen, and gonads, while Cyp19a was only expressed in the gonads and spleen. All-female Southern catfish fry were treated with fadrozole (F), tamoxifen (TAM), and 17β-estradiol (E2) respectively, from 5 to 25 days after hatching (dah). The expression levels of these genes were measured at 65 dah. In the F-, TAM-, and FTAM-treated groups, Dmrt1a and Dmrt1b were up-regulated in the gonad, whereas Foxl2 and Cyp19a were down-regulated, while the expression of Cyp19b in the gonad remained unchanged. Furthermore, down-regulation of Foxl2 and Cyp19b was also detected in the brain. In the E2-treated group, Dmrt1a and Dmrt1b were down-regulated to an undetectable level in the gonad, whereas Foxl2 and Cyp19b were up-regulated in the brain. Consistent with the observed changes in the expressions of these genes, 56, 70, and 80% sex-reversed male individuals were obtained in the F-, TAM-, and F + TAM-treated groups respectively. These results indicate the significant roles of Dmrt1, Foxl2, and Cyp19 in the sex differentiation of Southern catfish.


Endocrinology ◽  
2009 ◽  
Vol 150 (7) ◽  
pp. 3291-3300 ◽  
Author(s):  
Jing Liu ◽  
Eun-Sil Park ◽  
Misung Jo

Runt-related transcription factor 1 (RUNX1), a transcription factor, is transiently induced by the LH surge and regulates gene expression in periovulatory granulosa cells. Potential binding sites for RUNX are present in the 5′-flanking region of the Ptgs2 (prostaglandin-endoperoxide synthase 2) gene. Periovulatory Ptgs2 expression is essential for ovulation. In the present study, we investigated the role of RUNX1 in mediating the LH-induced expression of Ptgs2 in periovulatory granulosa cells. We first determined whether the suppression of Runx1 expression or activity affects Ptgs2 expression using cultured preovulatory granulosa cells isolated from immature rat ovaries primed with pregnant mare serum gonadotropin for 48 h. Knockdown of human chorionic gonadotropin-induced Runx1 expression by small interfering RNA or inhibition of endogenous RUNX activities by dominant-negative RUNX decreased human chorionic gonadotropin or agonist-stimulated Ptgs2 expression and transcriptional activity of Ptgs2 promoter reporter constructs. Results from chromatin immunoprecipitation assays revealed in vivo binding of endogenous RUNX1 to the Ptgs2 promoter region in rat periovulatory granulosa cells. Direct binding of RUNX1 to two RUNX-binding motifs in the Ptgs2 promoter region was confirmed by EMSA. The mutation of these two binding motifs resulted in decreased transcriptional activity of Ptgs2 promoter reporter constructs in preovulatory granulosa cells. Taken together, these findings provide experimental evidence that the LH-dependent induction of Ptgs2 expression results, in part, from RUNX1-mediated transactivation of the Ptgs2 promoter. The results of the present study assign potential significance for LH-induced RUNX1 in the ovulatory process via regulating Ptgs2 gene expression.


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