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Anna Doshina, Florian Gourgue, Michiho Onizuka, Remi Opsomer, Peng Wang, Kunie Ando, Bernadette Tasiaux, Ilse Dewachter, Pascal Kienlen-Campard, Jean-Pierre Brion, Philippe Gailly, Jean-Noël Octave, Nathalie Pierrot
The amyloid precursor protein (APP) modulates synaptic activity, resulting from the fine tuning of excitatory and inhibitory neurotransmission. GABAergic inhibitory neurotransmission is affected by modifications in intracellular chloride concentrations regulated by Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) and neuronal K(+)-Cl(-) cotransporter 2 (KCC2), allowing entrance and efflux of chloride, respectively. Modifications in NKCC1 and KCC2 expression during maturation of cortical cells induce a shift in GABAergic signaling...
March 23, 2017: Scientific Reports
Jacqueline R Hwang, Chung-Lin Chou, Barbara Medvar, Mark A Knepper, Hyun Jun Jung
The gene encoding the aquaporin-2 water channel is regulated transcriptionally in response to vasopressin. In the renal collecting duct, vasopressin stimulates the nuclear translocation and phosphorylation (at Ser552) of β-catenin, a multifunctional protein that acts as a transcriptional co-regulator in the nucleus. The purpose of this study was to identify β-catenin interacting proteins that may be involved in transcriptional regulation in rat inner medullary collecting duct (IMCD) cells using both experimental and computational approaches...
March 15, 2017: American Journal of Physiology. Renal Physiology
Jose A Viscarra, Yuhui Wang, Il-Hwa Hong, Hei Sook Sul
De novo lipogenesis is precisely regulated by nutritional and hormonal conditions. The genes encoding various enzymes involved in this process, such as fatty acid synthase (FASN), are transcriptionally activated in response to insulin. We showed that USF1, a key transcription factor for FASN activation, directly interacted with the Mediator subunit MED17 at the FASN promoter. This interaction recruited Mediator, which can bring POL II and other general transcription machinery to the complex. Moreover, we showed that MED17 was phosphorylated at Ser(53) by casein kinase 2 (CK2) in the livers of fed mice or insulin-stimulated hepatocytes, but not in the livers of fasted mice or untreated hepatocytes...
February 21, 2017: Science Signaling
Ryuichi Majima, Keiko Shindoh, Toyofumi Yamaguchi, Naoki Inoue
Previously we established reporter cell lines for human cytomegalovirus (HCMV) and varicella zoster virus (VZV) and identified several antiviral compounds against these viruses using the reporter cells. In this study, we found that one of the identified anti-HCMV compounds, a thienylcarboxamide derivative (coded as 133G4), was effective against not only HCMV but also VZV. The following findings indicate that 133G4 inhibits the activation of early gene promoters by HCMV IE2 and VZV IE62: i) 133G4 decreased the expression of HCMV early and late genes but not that of HCMV IE1/IE2 in HCMV-infected cells, ii) 133G4 inhibited the activation of several HCMV early gene promoters of transiently-transfected plasmids in HCMV-infected cells, and iii) in transient transfection assays, 133G4 decreased the activation of HCMV (or VZV) early gene promoters by HCMV IE2 (or VZV IE62) in the absence of other viral protein expression...
April 2017: Antiviral Research
Xiao-Tong Hu, Bing-Lin Zhu, Li-Ge Zhao, Jing-Wen Wang, Lu Liu, Yu-Jie Lai, Ling He, Xiao-Juan Deng, Guo-Jun Chen
ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) is the α-secretase that is involved in APP (β-amyloid precursor protein) processing. Enhancement of the nonamyloidogenic APP pathway by ADAM10 provides therapeutic potential for Alzheimer's disease (AD). By using high-throughput screening that targeted ADAM10, we determined that apicidin-an inhibitor of HDACs (histone deacetylases)-significantly increased mRNA and protein levels of ADAM10 in SH-SY5Y cells. A luciferase assay revealed that the nucleotides -444 to -300 in the ADAM10 promoter were sufficient to mediate this effect...
December 21, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Verena Vanessa Emmerling, Simon Fischer, Michael Kleemann, René Handrick, Stefan Kochanek, Kerstin Otte
MicroRNAs (miRNAs) are small non-coding RNAs that constitute a fundamental part of post-transcriptional gene regulation in mammalian cells. We have recently identified the intronic miR-483, which functions as an important regulator of protein synthesis during mild hypothermia in human and rodent cells. Since only very little is known about transcriptional regulation of intronic miRNAs and their host genes, we thoroughly investigated the regulation of miR-483 expression and its host gene IGF2 in HeLa cells. We demonstrate that miR-483 is regulated and expressed independently of its host gene IGF2 during mild hypothermia...
September 28, 2016: International Journal of Biochemistry & Cell Biology
Y-Q Ren, Q-H Li, L-B Liu
OBJECTIVE: The activation of TGF-β signaling contributes to abnormal EMT process and upstream stimulatory family1 (USF1) was recently found to activate the expression of TGF-β. However, the specific role of USF1 in melanoma has never been explored. MATERIALS AND METHODS: The expression of USF1 was analyzed using real-time PCR and Western blot. The changes of cell morphology were observed under a microscope. Cell migration was determined using in vitro scratch test...
September 2016: European Review for Medical and Pharmacological Sciences
Syed Khund-Sayeed, Ximiao He, Timothy Holzberg, Jun Wang, Divya Rajagopal, Shriyash Upadhyay, Stewart R Durell, Sanjit Mukherjee, Matthew T Weirauch, Robert Rose, Charles Vinson
We evaluated DNA binding of the B-HLH family members TCF4 and USF1 using protein binding microarrays (PBMs) containing double-stranded DNA probes with cytosine on both strands or 5-methylcytosine (5mC) or 5-hydroxymethylcytosine (5hmC) on one DNA strand and cytosine on the second strand. TCF4 preferentially bound the E-box motif (CAN|NTG) with strongest binding to the 8-mer CAG|GTGGT. 5mC uniformly decreases DNA binding of both TCF4 and USF1. The bulkier 5hmC also inhibited USF1 binding to DNA. In contrast, 5hmC dramatically enhanced TCF4 binding to E-box motifs ACAT|GTG and ACAC|GTG, being better bound than any 8-mer containing cytosine...
September 12, 2016: Integrative Biology: Quantitative Biosciences From Nano to Macro
Ravindra Gujar, Neeraj Maurya, Vinod Yadav, Mamta Gupta, Saurabh Arora, Neeraj Khatri, Pradip Sen
The enhanced expression of T cell Ig and mucin protein-3 (TIM-3) on tumor-associated dendritic cells (DCs) attenuates antitumor effects of DNA vaccines. To identify a potential target (or targets) for reducing TIM-3 expression on tumor-associated DCs, we explored the molecular mechanisms regulating TIM-3 expression. In this study, we have identified a novel signaling pathway (c-Src→Bruton's tyrosine kinase→transcription factors Ets1, Ets2, USF1, and USF2) necessary for TIM-3 upregulation on DCs. Both IL-10 and TGF-β, which are produced in the tumor microenvironment, upregulated TIM-3 expression on DCs via this pathway...
September 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Ying Li, Vincent P Schulz, Changwang Deng, Guangyao Li, Yong Shen, Betsabeh K Tusi, Gina Ma, Jared Stees, Yi Qiu, Laurie A Steiner, Lei Zhou, Keji Zhao, Jörg Bungert, Patrick G Gallagher, Suming Huang
The modulation of chromatin structure is a key step in transcription regulation in mammalian cells and eventually determines lineage commitment and differentiation. USF1/2, Setd1a and NURF complexes interact to regulate chromatin architecture in erythropoiesis, but the mechanistic basis for this regulation is hitherto unknown. Here we showed that Setd1a and NURF complexes bind to promoters to control chromatin structural alterations and gene activation in a cell context dependent manner. In human primary erythroid cells USF1/2, H3K4me3 and the NURF complex were significantly co-enriched at transcription start sites of erythroid genes, and their binding was associated with promoter/enhancer accessibility that resulted from nucleosome repositioning...
September 6, 2016: Nucleic Acids Research
Lucie Hyrsova, Tomas Smutny, Alejandro Carazo, Stefan Moravcik, Jana Mandikova, Frantisek Trejtnar, Sabine Gerbal-Chaloin, Petr Pavek
BACKGROUND AND PURPOSE: The organic cation transporter 1 (OCT1) transports cationic drugs into hepatocytes. The high hepatic expression of OCT1 is controlled by the HNF4α and USF transcription factors. Pregnane X receptor (PXR) mediates induction of the principal xenobiotic metabolizing enzymes and transporters in the liver. Here, we have assessed the down-regulation of OCT1 expression by PXR activation. EXPERIMENTAL APPROACH: We used primary human hepatocytes and related cell lines to measure OCT1 expression and activity, by assaying MPP(+) accumulation...
May 2016: British Journal of Pharmacology
Pirkka-Pekka Laurila, Jarkko Soronen, Sander Kooijman, Saara Forsström, Mariëtte R Boon, Ida Surakka, Essi Kaiharju, Claudia P Coomans, Sjoerd A A Van Den Berg, Anu Autio, Antti-Pekka Sarin, Johannes Kettunen, Emmi Tikkanen, Tuula Manninen, Jari Metso, Reija Silvennoinen, Krista Merikanto, Maija Ruuth, Julia Perttilä, Anne Mäkelä, Ayaka Isomi, Anita M Tuomainen, Anna Tikka, Usama Abo Ramadan, Ilkka Seppälä, Terho Lehtimäki, Johan Eriksson, Aki Havulinna, Antti Jula, Pekka J Karhunen, Veikko Salomaa, Markus Perola, Christian Ehnholm, Miriam Lee-Rueckert, Miranda Van Eck, Anne Roivainen, Marja-Riitta Taskinen, Leena Peltonen, Eero Mervaala, Anu Jalanko, Esa Hohtola, Vesa M Olkkonen, Samuli Ripatti, Petri T Kovanen, Patrick C N Rensen, Anu Suomalainen, Matti Jauhiainen
USF1 (upstream stimulatory factor 1) is a transcription factor associated with familial combined hyperlipidemia and coronary artery disease in humans. However, whether USF1 is beneficial or detrimental to cardiometabolic health has not been addressed. By inactivating USF1 in mice, we demonstrate protection against diet-induced dyslipidemia, obesity, insulin resistance, hepatic steatosis, and atherosclerosis. The favorable plasma lipid profile, including increased high-density lipoprotein cholesterol and decreased triglycerides, was coupled with increased energy expenditure due to activation of brown adipose tissue (BAT)...
January 27, 2016: Science Translational Medicine
Yanli Zeng, Hui Li, Xiaoju Zhang, Jia Shang, Yi Kang
Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G, A3G) exert antiviral defense as an important factor of innate immunity. A variety of cytokines such as IFN-γ、IL2、IL15、IL7 could induce the transcription of A3G. However, the regulation of other nuclear factor on the transcription of A3G have not been reported at the present. To gain new insights into the transcriptional regulation of this restriction factor, we cloned and characterized the promoter region of A3G and investigate the modulation of USF1 gene on the transcription of A3G...
January 29, 2016: Biochemical and Biophysical Research Communications
Tomoyuki Yamanaka, Asako Tosaki, Masaru Kurosawa, Tomomi Shimogori, Nobutaka Hattori, Nobuyuki Nukina
UNLABELLED: The upstream transcription factors (USFs) USF1 and USF2 are ubiquitously expressed transcription factors that are characterized by a conserved basic helix-loop-helix/leucine zipper DNA-binding domain. They form homo- or heterodimers, and recognize E-box motifs to modulate gene expression. They are known to regulate diverse cellular functions, including the cell cycle, immune responses and glucose/lipid metabolism, but their roles in neuronal cells remain to be clarified. Here, we performed chromatin immunoprecipitation of USF1 from mouse brain cortex...
March 2016: FEBS Journal
Chunhua Cao, Jianhua Chen, Chengqi Lyu, Jia Yu, Wei Zhao, Yi Wang, Derong Zou
This study was designed to explore the effects of tobacco smoke on gene expression through bioinformatics analyses. Gene expression profile GSE17913 was downloaded from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) in buccal mucosa tissues between 39 active smokers and 40 never smokers were identified. Gene Ontology Specifically, the DEG distribution in the pathway of Metabolism of xenobiotics by cytochrome P450 was shown in Fig 2[corrected] were performed, followed by protein-protein interaction (PPI) network, transcriptional regulatory network as well as miRNA-target regulatory network construction...
2015: PloS One
Sarah Spohrer, Elitsa Y Dimova, Thomas Kietzmann, Mathias Montenarh, Claudia Götz
The functions of the upstream stimulatory factors USF1 and USF2 are, like those of other transcription factors, regulated by reversible phosphorylation. Besides many other kinases also protein kinase CK2 phosphorylates USF1 but not USF2. In a yeast-two-hybrid screen, however, the non-catalytic CK2β subunit of CK2 was identified as a binding partner of USF2. This surprising observation prompted us to investigate the CK2/USF interaction in more detail in the present study. By using immunofluorescence analyses as well as co-immunoprecipitations we found that USF1 and USF2 bound to CK2α and CK2β exclusively in the nucleus, though CK2β and to a minor amount CK2α were also present in the cytoplasm...
February 2016: Cellular Signalling
Jisu Park, Heesung Chung, Seung Hyun Bang, Ah-Reum Han, Eun-Kyoung Seo, Sung Eun Chang, Duk-Hee Kang, Eok-Soo Oh
We investigated the potential melanogenic effect of compounds from Zingiber cassumunar Roxb. Our data revealed that chloroform-soluble extract of Z. cassumunar enhanced melanin synthesis in B16F10 melanoma cells. Among the components of the chloroform extract, (E)-4-(3,4-dimethoxyphenyl)but-3-en-1-ol (DMPB) increased melanogenesis in both B16F10 cells and human primary melanocytes. In B16F10 cells, DMPB enhanced the activation of ERK and p38, and the level of tyrosinase. Although the level of microphthalmia-associated transcription factor was unchanged in DMPB-treated B16F10 cells, DMPB increased levels and nuclear localization of upstream stimulating factor-1 (USF1)...
2015: PloS One
Karolina Lech, Katrin Ackermann, Victoria L Revell, Oscar Lao, Debra J Skene, Manfred Kayser
The identification and investigation of novel clock-controlled genes (CCGs) has been conducted thus far mainly in model organisms such as nocturnal rodents, with limited information in humans. Here, we aimed to characterize daily and circadian expression rhythms of CCGs in human peripheral blood during a sleep/sleep deprivation (S/SD) study and a constant routine (CR) study. Blood expression levels of 9 candidate CCGs (SREBF1, TRIB1, USF1, THRA1, SIRT1, STAT3, CAPRIN1, MKNK2, and ROCK2), were measured across 48 h in 12 participants in the S/SD study and across 33 h in 12 participants in the CR study...
February 2016: Journal of Biological Rhythms
Chen-Chia Hung, Chung-Wen Kuo, Wen-Hung Wang, Tzu-Hsuan Chang, Pey-Jium Chang, Li-Kwan Chang, Shih-Tung Liu
During its lytic cycle, Epstein-Barr virus (EBV) expresses Rta, a factor encoded by BRLF1 that activates the transcription of viral lytic genes. We found that upstream stimulating factor (USF) binds to E1, one of the five E boxes located at - 79 in the BRLF1 promoter (Rp), to activate BRLF1 transcription. Furthermore, Rta was shown to interact with USF1 in coimmunoprecipitation and glutathione S-transferase (GST)-pulldown assays, and confocal laser-scanning microscopy further confirmed that these two proteins colocalize in the nucleus...
September 2015: Journal of General Virology
C Cerutti, C Z Paultre, M P Gustin, O Lohez, P Feugier, J Y Li, G Bricca
OBJECTIVE: During atherogenesis, vascular smooth muscle cells (VSMCs) undergo a phenotypic modulation leading to migration and loss of contractility. Here we propose a gene regulatory network specific of the contractile phenotype of the carotid VSMCs from transcriptomic data. DESIGN AND METHOD: Human carotid atheroma plaque (ATH, Stary>4) and nearby macroscopically intact tissue (MIT, Stary<3) of 32 patients were analysed by microarrays (Affymetrix HuGene-1...
June 2015: Journal of Hypertension
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