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Kai Zhu, Shang Li, Jiansheng Liu, Yan Hong, Zi-Jiang Chen, Yanzhi Du
Polycystic ovary syndrome, a common condition characterized by endocrine dysfunction, menstrual irregularity, anovulation, and polycystic ovaries, affects 5%-7% of reproductive-age women. RAB5B, which is identified by a genome-wide association study as a risk locus for this syndrome, encodes a small GTPase involved in control of receptor internalization and early endosome fusion. We found that RAB5A mRNA levels in luteinized granulosa cells of obese patients with polycystic ovary syndrome were lower than in those of obese women without the syndrome...
April 6, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
Heather N Carter, Marion Pauly, Liam D Tryon, David A Hood
Mitochondrial impairments are often noted in aged skeletal muscle. The transcriptional coactivator PGC-1α is integral to maintaining mitochondria, and its expression declines in aged muscle. It remains unknown whether this is due to a transcriptional deficit during aging. Our study examined PGC-1α transcription in muscle from young and old F344BN rats. Using a rat PGC-1α promoter-reporter construct, we found that PGC-1α transcription was reduced by ~65% in aged TA muscle, accompanied by decreases in PGC-1α mRNA and transcript stability...
March 15, 2018: Journal of Applied Physiology
Jun Guo, Weiwei Fang, Libo Sun, Yonggang Lu, Lin Dou, Xiuqing Huang, Weiqing Tang, Liqing Yu, Jian Li
Ultraconserved (uc) RNAs, a class of long non-coding RNAs (lncRNAs), are conserved across humans, mice, and rats, but the physiological significance and pathological role of ucRNAs is largely unknown. Here we show that uc.372 is upregulated in the livers of db/db mice, HFD-fed mice, and NAFLD patients. Gain-of-function and loss-of-function studies indicate that uc.372 drives hepatic lipid accumulation in mice by promoting lipogenesis. We further demonstrate that uc.372 binds to pri-miR-195/pri-miR-4668 and suppresses maturation of miR-195/miR-4668 to regulate expression of genes related to lipid synthesis and uptake, including ACC, FAS, SCD1, and CD36...
February 9, 2018: Nature Communications
Cristina T Vicente, Joana A Revez, Manuel A R Ferreira
Twenty-five genome-wide association studies (GWAS) of asthma were published between 2007 and 2016, the largest with a sample size of 157242 individuals. Across these studies, 39 genetic variants in low linkage disequilibrium (LD) with each other were reported to associate with disease risk at a significance threshold of P <5 × 10-8 , including 31 in populations of European ancestry. Results from analyses of the UK Biobank data ( n =380 503) indicate that at least 28 of the 31 associations reported in Europeans represent true-positive findings, collectively explaining 2...
December 2017: Clinical & Translational Immunology
H Ye, X J Liu, Y Hui, Y H Liang, C H Li, Q Wan
This study was supposed to investigate the correlation between the functional single nucleotide polymorphisms (SNPs) (rs2516839 and rs3737787) in USF1 gene and the efficacy and safety of paclitaxel-based chemotherapy and prognosis in the treatment of ovarian cancer (OC). In total 100 OC patients were selected and divided into the sensitive group and the resistantgroup according to the tumor response to paclitaxel-based chemotherapy after surgery, and the incidence of observed and recorded toxic reaction. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was applied to test the polymorphisms of rs2516839 and rs3737787 in USF1 gene after extraction of DNA...
2018: Neoplasma
Sarah Spohrer, Rebecca Groß, Lisa Nalbach, Lisa Schwind, Heike Stumpf, Michael D Menger, Emmanuel Ampofo, Mathias Montenarh, Claudia Götz
Glucose homeostasis is regulated by insulin, which is produced in the β-cells of the pancreas. The synthesis of insulin is controlled by several transcription factors including PDX-1, USF1 and USF2. Both, PDX-1 and USF1 were identified as substrates for protein kinase CK2. Here, we have analysed the interplay of PDX-1, USF1 and CK2 in the regulation of PDX-1 gene transcription. We found that the PDX-1 promoter is dose-dependently transactivated by PDX-1 and transrepressed by USF1. With increasing glucose concentrations the transrepression of the PDX-1 promoter by USF1 is successively abrogated...
November 27, 2017: Scientific Reports
Sugantha Priya Elayapillai, Dhanaraj Teekaraman, Raja Singh Paulraj, Arunakaran Jagadeesan
The study was conducted to investigate the protective role of α-tocopherol against polychlorinated biphenyls (PCBs) induced effect in Sertoli cell function of F1 prepuberal rats. Dams were grouped into six; each group consists of six animals. Group 1-control treated with corn oil as vehicle, group II- 0.5mgPCBs/kg bw/day, group III- 0.5mgPCBs/kg bw/day with α-tocopherol (50mg α-tocopherol/kg bw/day), group IV- 1mgPCBs/kg bwt/day, group V- 1mgPCBs/kg bw/day with α-tocopherol (50mg α-tocopherol/kg bw/day) and group VI - α-tocopherol alone treated orally from postpartum day1-20...
October 2, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
Libo Sa, Yan Li, Lini Zhao, Yunhui Liu, Ping Wang, Libo Liu, Zhen Li, Jun Ma, Heng Cai, Yixue Xue
Homeobox transcript antisense intergenic RNA (HOTAIR), as a long non-coding RNA (lncRNA), has been considered to play critical roles in the biological properties of various tumors. The purposes of this study were to investigate the role and possible molecular mechanisms of HOTAIR in regulating the permeability of blood tumor barrier (BTB) in vitro. Our present study elucidated that the expressions of HOTAIR and upstream stimulatory factor 1 (USF1) was up-regulated, but miR-148b-3p was down-regulated in glioma microvascular endothelial cells (GECs)...
2017: Frontiers in Molecular Neuroscience
F Pepe, S Pagotto, S Soliman, C Rossi, P Lanuti, C Braconi, R Mariani-Costantini, R Visone, A Veronese
The miR-483-3p is upregulated in several tumors, including liver tumors, where it inhibits TP53-dependent apoptosis by targeting the pro-apoptotic gene BBC3/PUMA. The transcriptional regulation of the miR-483-3p could be driven by the β-catenin/USF1 complex, independently from its host gene IGF2, and we previously demonstrated that in HepG2 hepatoblastoma cells carrying wild-type TP53 the upregulation of the miR-483-3p overcomes the antitumoral effects of the tumor-suppressor miR-145-5p by a mechanism involving cellular glucose availability...
May 8, 2017: Oncogenesis
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 Ser(552)) of β-catenin, a multifunctional protein that acts as a transcriptional coregulator in the nucleus. The purpose of this study was to identify β-catenin-interacting proteins that might be involved in transcriptional regulation in rat inner medullary collecting duct (IMCD) cells, using experimental and computational approaches...
July 1, 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 Ser53 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...
April 2017: 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...
November 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
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