A repressive role of enhancer of zeste homolog 2 in 11β-hydroxysteroid dehydrogenase type 2 expression in the human placenta

The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which acts as a placental glucocorticoid barrier, is silenced in cytotrophoblasts but substantially up-regulated during syncytialization. However, the repressive mechanism of 11β-HSD2 expression before syncytialization and how this repression is lifted during syncytialization remain mostly unresolved. Here we found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 at the promoter of the 11β-HSD2 gene. Further studies revealed that, upon syncytialization, human chorionic gonadotropin reduced the phosphorylation of retinoblastoma protein (pRB) via activation of the cAMP/PKA pathway, which sequesters E2F transcription factor 1 (E2F1), the transcription factor for EZH2 expression. As a result of inactivation of the pRB-E2F1-EZH2 pathway, the repressive marker trimethylation of histone H3 lysine 27 at the 11β-HSD2 promoter is removed, which leads to the robust expression of 11β-HSD2 during syncytialization.

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Gender bias in the genetic vulnerability towards type 2 diabetes and diabetic nephropathy: Role of forkhead box Protein3 transcription factor gene variants

Gene ◽

10.1016/j.gene.2021.145426 ◽

2021 ◽

Vol 774 ◽

pp. 145426

Author(s):

Swetha Chikoti ◽

Umme Najiya Mahwish ◽

Sree Bhushan Raju ◽

Sumanlatha Gaddam ◽

Parveen Jahan

Keyword(s):

Type 2 Diabetes ◽

Transcription Factor ◽

Diabetic Nephropathy ◽

Gender Bias ◽

Gene Variants ◽

Transcription Factor Gene ◽

Factor Gene ◽

Forkhead Box

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E2F transcription factor-1 regulates oxidative metabolism

Nature Cell Biology ◽

10.1038/ncb2309 ◽

2011 ◽

Vol 13 (9) ◽

pp. 1146-1152 ◽

Cited By ~ 146

Author(s):

Emilie Blanchet ◽

Jean-Sébastien Annicotte ◽

Sylviane Lagarrigue ◽

Victor Aguilar ◽

Cyrielle Clapé ◽

...

Keyword(s):

Transcription Factor ◽

Oxidative Metabolism ◽

E2f Transcription Factor ◽

Transcription Factor 1

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The nucleoplasmic interactions among Lamin A/C-pRB-LAP2α-E2F1 are modulated by dexamethasone

Scientific Reports ◽

10.1038/s41598-021-89608-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anastasia Ricci ◽

Sara Orazi ◽

Federica Biancucci ◽

Mauro Magnani ◽

Michele Menotta

Keyword(s):

Gene Expression ◽

Cell Cycle Progression ◽

Regulation Of Gene Expression ◽

Lamin A ◽

Wild Type ◽

Cycle Progression ◽

C Dynamics ◽

E2f Transcription Factor ◽

Transcription Factor 1

AbstractAtaxia telangiectasia (AT) is a rare genetic neurodegenerative disease. To date, there is no available cure for the illness, but the use of glucocorticoids has been shown to alleviate the neurological symptoms associated with AT. While studying the effects of dexamethasone (dex) in AT fibroblasts, by chance we observed that the nucleoplasmic Lamin A/C was affected by the drug. In addition to the structural roles of A-type lamins, Lamin A/C has been shown to play a role in the regulation of gene expression and cell cycle progression, and alterations in the LMNA gene is cause of human diseases called laminopathies. Dex was found to improve the nucleoplasmic accumulation of soluble Lamin A/C and was capable of managing the large chromatin Lamin A/C scaffolds contained complex, thus regulating epigenetics in treated cells. In addition, dex modified the interactions of Lamin A/C with its direct partners lamin associated polypeptide (LAP) 2a, Retinoblastoma 1 (pRB) and E2F Transcription Factor 1 (E2F1), regulating local gene expression dependent on E2F1. These effects were differentially observed in both AT and wild type (WT) cells. To our knowledge, this is the first reported evidence of the role of dex in Lamin A/C dynamics in AT cells, and may represent a new area of research regarding the effects of glucocorticoids on AT. Moreover, future investigations could also be extended to healthy subjects or to other pathologies such as laminopathies since glucocorticoids may have other important effects in these contexts as well.

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E2F transcription factor 1 (E2F1) enhances the proliferation, invasion and EMT of trophoblast cells by binding to Zinc Finger E-Box Binding Homeobox 1 (ZEB1)

Bioengineered ◽

10.1080/21655979.2021.2023793 ◽

2022 ◽

Vol 13 (2) ◽

pp. 2360-2370

Author(s):

Han Gong ◽

Fan Lu ◽

Xiaoling Zeng ◽

Qing Bai

Keyword(s):

Transcription Factor ◽

Zinc Finger ◽

Trophoblast Cells ◽

E Box ◽

E2f Transcription Factor ◽

Transcription Factor 1

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Clinical Implication of E2F Transcription Factor 1 in Hepatocellular Carcinoma Tissues

Cancer Biotherapy & Radiopharmaceuticals ◽

10.1089/cbr.2020.4342 ◽

2021 ◽

Author(s):

Wang-Yang Ye ◽

Hui-Ping Lu ◽

Jian-Di Li ◽

Gang Chen ◽

Rong-Quan He ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Transcription Factor ◽

Clinical Implication ◽

E2f Transcription Factor ◽

Transcription Factor 1

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Role of an α-helical bulge in the yeast heat shock transcription factor 1 1Edited by F. E. Cohen

Journal of Molecular Biology ◽

10.1006/jmbi.1999.3357 ◽

2000 ◽

Vol 295 (3) ◽

pp. 393-409 ◽

Cited By ~ 22

Author(s):

Jeanne A Hardy ◽

Scott T.R Walsh ◽

Hillary C.M Nelson

Keyword(s):

Transcription Factor ◽

Heat Shock ◽

Heat Shock Transcription Factor ◽

Transcription Factor 1

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Increased Expression of RUNX1 in Liver Correlates with NASH Activity Score in Patients with Non-Alcoholic Steatohepatitis (NASH)

Cells ◽

10.3390/cells8101277 ◽

2019 ◽

Vol 8 (10) ◽

pp. 1277 ◽

Cited By ~ 4

Author(s):

Kaur ◽

Rawal ◽

Siddiqui ◽

Rohilla ◽

Sharma ◽

...

Keyword(s):

Transcription Factor ◽

Activity Score ◽

Over Expression ◽

Alcoholic Steatohepatitis ◽

Related Transcription Factor ◽

Underlying Mechanisms ◽

Parenchymal Cells ◽

Transcription Factor 1

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.

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