A Cell-Permeable Synthetic Transcription Factor Mimic

2007 ◽  
Vol 46 (16) ◽  
pp. 2865-2868 ◽  
Author(s):  
Xiangshu Xiao ◽  
Peng Yu ◽  
Hyun-Suk Lim ◽  
Devanjan Sikder ◽  
Thomas Kodadek
Keyword(s):  
Transcription Factor ◽  
A Cell

scholarly journals Syntaxin 1A Gene Is Negatively Regulated in a Cell/Tissue Specific Manner by YY1 Transcription Factor, Which Binds to the −183 to −137 Promoter Region Together with Gene Silencing Factors Including Histone Deacetylase

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 146
Author(s):  
Takahiro Nakayama ◽  
Toshiyuki Fukutomi ◽  
Yasuo Terao ◽  
Kimio Akagawa
Keyword(s):  
Transcription Factor ◽  
Gene Silencing ◽  
Protein Complex ◽  
Promoter Region ◽  
Neuronal Cell ◽  
Syntaxin 1A ◽  
Tissue Specific ◽  
Cell Tissue ◽  
Specific Manner ◽  
A Cell

The HPC-1/syntaxin 1A (Stx1a) gene, which is involved in synaptic transmission and neurodevelopmental disorders, is a TATA-less gene with several transcription start sites. It is activated by the binding of Sp1 and acetylated histone H3 to the −204 to +2 core promoter region (CPR) in neuronal cell/tissue. Furthermore, it is depressed by the association of class 1 histone deacetylases (HDACs) to Stx1a–CPR in non-neuronal cell/tissue. To further clarify the factors characterizing Stx1a gene silencing in non-neuronal cell/tissue not expressing Stx1a, we attempted to identify the promoter region forming DNA–protein complex only in non-neuronal cells. Electrophoresis mobility shift assays (EMSA) demonstrated that the −183 to −137 OL2 promoter region forms DNA–protein complex only in non-neuronal fetal rat skin keratinocyte (FRSK) cells which do not express Stx1a. Furthermore, the Yin-Yang 1 (YY1) transcription factor binds to the −183 to −137 promoter region of Stx1a in FRSK cells, as shown by competitive EMSA and supershift assay. Chromatin immunoprecipitation assay revealed that YY1 in vivo associates to Stx1a–CPR in cell/tissue not expressing Stx1a and that trichostatin A treatment in FRSK cells decreases the high-level association of YY1 to Stx1a-CPR in default. Reporter assay indicated that YY1 negatively regulates Stx1a transcription. Finally, mass spectrometry analysis showed that gene silencing factors, including HDAC1, associate onto the −183 to −137 promoter region together with YY1. The current study is the first to report that Stx1a transcription is negatively regulated in a cell/tissue-specific manner by YY1 transcription factor, which binds to the −183 to −137 promoter region together with gene silencing factors, including HDAC.

scholarly journals A Banana PHD-Type Transcription Factor MaPHD1 Represses a Cell Wall-Degradation Gene MaXTH6 during Fruit Ripening

2017 ◽  
Vol 3 (5) ◽  
pp. 190-198 ◽  
Author(s):  
Wei WEI ◽  
Zhongqi FAN ◽  
Jianye CHEN ◽  
Jianfei KUANG ◽  
Wangjin LU ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Fruit Ripening ◽  
Cell Wall Degradation ◽  
A Cell

Abstract 643: Type-2 Cannabinoid Receptor Deficiency is Associated with Atherosclerotic Lesion Calcification in Ldlr-null Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Makenzie L Fulmer ◽  
Emilee Englehaupt ◽  
Chris Garst ◽  
Stacy Brown ◽  
Douglas Thewke
Keyword(s):  
Transcription Factor ◽  
Cannabinoid Receptor ◽  
Atherosclerotic Lesion ◽  
Increased Risk ◽  
Calcified Plaque ◽  
En Face ◽  
Related Transcription Factor ◽  
A Cell ◽  
Complex Signaling

Background: Calcification of atherosclerotic plaques is associated with vulnerability to rupture and increased risk of myocardial infarction. The mechanism of plaque calcification is unclear, but has been shown to be a cell-mediated process involving complex signaling pathways affecting the osteogenic transcription factor Runt-related transcription factor 2 (Runx2). The type-2 cannabinoid receptor (CB2) modulates processes involved in bone remodeling and our prior studies determined that CB2 alters the composition of early lesions in hyperlipidemic Ldlr -/- mice; however, the function of CB2 in plaque calcification is unknown. Therefore, we tested the hypothesis that CB2 modulates plaque calcification by evaluating the effects of systemic CB2 gene deletion on lesion calcification and aortic expression of Runx2 in Ldlr -/- mice. Results: Groups (n≥8) of 8-week old CB2 +/+ Ldlr -/- (WT) and CB2 -/- Ldlr -/- (CB2 -/- ) mice were fed a high fat diet (HFD) for up to 24 weeks. Standard blood plasma analysis showed no difference in HFD-induced hyperlipidemia between WT and CB2 -/- mice. Aortic levels of endocannabinoids, anandamide and 2-archidonylglycerol, were significantly elevated after 12 weeks of HFD feeding as determined by LC-MS/MS. En face analysis revealed the extent of atherosclerosis in the aortic arch and thoracic aorta did not differ between WT and CB2 -/- mice, but was ~1.9-fold greater in the abdominal aortas of CB2 -/- mice (17.0±1.3% vs 9.0±1.3%, p=0.002). Calcification of aortic root lesions was ~2.3 fold greater in CB2 -/- mice compared to WT mice (12.9±1.1% vs 5.6±1.2%, p=0.002) as revealed by von Kossa staining. Western blot analysis showed significantly increased expression of Runx2 in aortas of WT mice compared to CB2 -/- after 20 weeks of HFD (2.55±0.25 fold, p<0.05). Conclusion: Systemic CB2 deficiency enhances lesion calcification and is associated with altered aortic expression of Runx2. These results provide novel mechanistic insights into the function of CB2 signaling in the pathogenesis of atherosclerosis and vascular calcification that may lead to the development of therapies aimed at stabilizing calcified plaque.

scholarly journals Ligand-dependent and -independent activation of the transcription factor γRF-1 in a cell-free system

1995 ◽  
Vol 310 (2) ◽  
pp. 461-467 ◽  
Author(s):  
C A Feghali ◽  
T M Wright
Keyword(s):  
Transcription Factor ◽  
Tyrosine Phosphatase ◽  
Cell Fractionation ◽  
Dependent Manner ◽  
Sodium Orthovanadate ◽  
Ifn Gamma ◽  
Free System ◽  
Cell Free System ◽  
A Cell

gamma RF-1 is a recently identified transcription factor induced by interferon-gamma (IFN-gamma) which binds to a unique palindromic enhancer, gamma RE-1, in the promoter of the mig gene. This paper describes the ligand-dependent and ligand-independent activation of gamma RF-1 in a cell-free system. gamma RF-1 activity was induced by IFN-gamma in a time-dependent manner from 5 to 60 min in lysates prepared from the human monocytic leukaemia line THP-1 and the human epidermoid carcinoma line A431. The activation of gamma RF-1 in vitro required both ATP and an inhibitor of tyrosine phosphatases (sodium orthovanadate or pervanadate). In the presence of limiting concentrations (micromolar) of ATP, activation was also dependent upon stimulation with IFN-gamma, whereas at millimolar concentrations of ATP, gamma RF-1 was activated by either sodium orthovanadate or pervanadate in the absence of ligand. Based on cell fractionation studies, both membrane and cytosol components were essential for activation of gamma RF-1 in vitro. Consistent with a role for one or more tyrosine kinases in the activation of gamma RF-1, its DNA binding activity was blocked by monoclonal anti-phosphotyrosine antibodies and by the tyrosine kinase inhibitors genistein, lavendustin A and herbimycin A. A comparison with recently described pathways of IFN-mediated transcription factor regulation indicates that the in vitro activation of gamma RF-1 is unique, requiring both membrane and cytosol fractions and inhibition of endogenous tyrosine phosphatase activity.

scholarly journals Regulation of a Cell Type-specific Silencer in the Human Interleukin-3 Gene Promoter by the Transcription Factor YY1 and an AP2 Sequence-recognizing Factor

1999 ◽  
Vol 274 (38) ◽  
pp. 26661-26667 ◽  
Author(s):  
Jianping Ye ◽  
Howard A. Young ◽  
Xiaoying Zhang ◽  
Vince Castranova ◽  
Val Vallyathan ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Promoter ◽  
Cell Type ◽  
Interleukin 3 ◽  
A Cell ◽  
Cell Type Specific ◽  
Transcription Factor Yy1

scholarly journals Analogs of the Dopamine Metabolite 5,6-Dihydroxyindole Bind Directly to and Activate the Nuclear Receptor Nurr1 (NR4A2)

2021 ◽  
Author(s):  
Svetlana A. Kholodar ◽  
Geoffrey Lang ◽  
Wilian A. Cortopassi ◽  
Yoshie Iizuka ◽  
Harman S. Brah ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Substantia Nigra ◽  
Ligand Binding ◽  
Nuclear Receptor ◽  
Cell Population ◽  
Substantia Nigra Pars Compacta ◽  
Related Protein ◽  
Endogenous Dopamine ◽  
A Cell ◽  
Unstable Compound

The nuclear receptor-related protein, Nurr1, is a transcription factor critical for the development and maintenance of dopamine-producing neurons in the substantia nigra pars compacta, a cell population that progressively loses the ability to make dopamine and degenerates in Parkinson's disease. Recently, we demonstrated that Nurr1 binds directly to and is regulated by the endogenous dopamine metabolite 5,6-dihydroxyindole (DHI). Unfortunately, DHI is an unstable compound, and thus a poor tool for studying Nurr1 function. Here we report that 5-chloroindoe, an unreactive analog of DHI, binds directly to the Nurr1 ligand binding domain with micromolar affinity and stimulates the activity of Nurr1, including the transcription of genes governing the synthesis and packaging of dopamine.

scholarly journals The transcriptional corepressor CTBP-1 acts with the SOX family transcription factor EGL-13 to maintain AIA interneuron cell identity in C. elegans

2021 ◽  
Author(s):  
Josh Saul ◽  
Takashi Hirose ◽  
Robert Horvitz
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cell Fate ◽  
Transcriptional Corepressor ◽  
Cell Identity ◽  
C Elegans ◽  
Dna Binding Specificity ◽  
A Cell ◽  
Transcriptional Corepressors ◽  
And Function

Cell identity is characterized by a distinct combination of gene expression, cell morphology and cellular function established as progenitor cells divide and differentiate. Following establishment, cell identities can be unstable and require active and continuous maintenance throughout the remaining life of a cell. Mechanisms underlying the maintenance of cell identities are incompletely understood. Here we show that the gene ctbp-1, which encodes the transcriptional corepressor C-terminal binding protein-1 (CTBP-1), is essential for the maintenance of the identities of the two AIA interneurons in the nematode Caenorhabditis elegans. ctbp-1 is not required for the establishment of the AIA cell fate but rather functions cell-autonomously and can act in older worms to maintain proper AIA gene expression, morphology and function. From a screen for suppressors of the ctbp-1 mutant phenotype, we identified the gene egl-13, which encodes a SOX family transcription factor. We found that egl-13 regulates AIA function and aspects of AIA gene expression, but not AIA morphology. We conclude that the CTBP-1 protein maintains AIA cell identity in part by utilizing EGL-13 to repress transcriptional activity in the AIAs. More generally, we propose that transcriptional corepressors like CTBP-1 might be critical factors in the maintenance of cell identities, harnessing the DNA-binding specificity of transcription factors like EGL-13 to selectively regulate gene expression in a cell-specific manner.

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