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Bo Yan - One of the best experts on this subject based on the ideXlab platform.
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identification and functional analysis of Genetic variants in tbx5 Gene Promoter in patients with acute myocardial infarction
BMC Cardiovascular Disorders, 2019Co-Authors: Shuai Wang, Jie Zhang, Yexin Zhang, Shuchao Pang, Yinghua Cui, Jing Chen, Shufang Zhang, Bo YanAbstract:Coronary artery disease (CAD), including acute myocardial infarction (AMI), is a common complex disease. Although a great number of Genetic loci and variants for CAD have been identified, Genetic causes and underlying mechanisms remain largely unclear. Epidemiological studies have revealed that CAD incidence is strikingly higher in patients with congenital heart disease than that in normal population. T-box transcription factors play critical roles in embryonic development. In particular, TBX5 as a dosage-sensitive regulator is required for cardiac development and function. Thus, dysregulated TBX5 Gene expression may be involved in CAD development. TBX5 Gene Promoter was Genetically and functionally analysed in large groups of AMI patients (n = 432) and ethnic-matched healthy controls (n = 448). Six novel heterozygous DNA sequence variants (DSVs) in the TBX5 Gene Promoter (g.4100A > G, g.4194G > A, g.4260 T > C, g.4367C > A, g.4581A > G and g.5004G > T) were found in AMI patients, but in none of controls. These DSVs significantly changed the activity of TBX5 Gene Promoter in cultured cells (P G, g.4260 T > C and g.4581A > G) evidently modified the binding sites of unknown transcription factors. The DSVs identified in AMI patients may alter TBX5 Gene Promoter activity and change TBX5 level, contributing to AMI development as a rare risk factor.
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functional Genetic variants in the sirt5 Gene Promoter in acute myocardial infarction
Gene, 2018Co-Authors: Lu Chen, Haiyan Wang, Feng Gao, Jie Zhang, Yexin Zhang, Shuchao Pang, Yinghua Cui, Jian Yang, Bo YanAbstract:Coronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease. To date, Genetic causes for atherosclerosis remain largely unknown. It has recently been proposed that low frequency and rare Genetic variants may be the main causes. Mitochondrial sirtuins, SIRT3, SIRT4 and SIRT5, function as critical regulators of mitochondrial metabolism, oxidative stress and cell survival. We speculated that altered SIRT5 level resulting from DNA sequence variants (DSVs) within SIRT5 Gene regulatory regions may contribute to the CAD and AMI development. In this study, the SIRT5 Gene Promoter was Genetically and functionally analyzed in large cohorts of AMI patients (n = 381) and healthy controls (n = 391). A total of eleven DSVs and SNPs were found. Two novel heterozygous DSVs (g.13574131C>A and g.13574287G>C) and three heterozygous SNPs [g.13573450A>G (rs573515169), g.13574110G>A (rs2804924) and g.13574259G>C (rs112443954)] were identified only in AMI patients. The DSVs and SNPs significantly decreased the transcriptional activity of the SIRT5 Gene Promoter in both HEK-293 and H9c2 cells (P 0.05). Therefore, our data suggested that the DSVs and SNPs identified in AMI patients may change SIRT5 level by affecting activity of SIRT5 Gene Promoter, contributing to the AMI development as a risk factor.
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Genetic and functional analysis of the TBX3 Gene Promoter in indirect inguinal hernia.
Gene, 2014Co-Authors: Zhongqing Zhao, Qining Xing, Shuchao Pang, Xianyun Qin, Wenjun Tian, Lin Wang, Haihua Wang, Bo YanAbstract:Inguinal hernia is a common developmental disease in children and most cases are indirect inguinal hernia (IIH). Genetic factors have been suggested to play important roles in IIH. Although IIH has been observed in several human syndromes, Genetic causes and molecular mechanisms for IIH remain unknown. TBX3 is a member of the T-box family of transcription factors that are essential to the embryonic development. Human studies and animal experiments have demonstrated that TBX3 is required for the development of the heart, limbs, mammary glands and other tissues and organs. TBX3 Gene expression has been detected in human fibroblast and tissues of abdominal wall. We speculated that TBX3 may be involved in the IIH formation. Since TBX3 activity is highly dosage-sensitive, a TBX3 Gene Promoter was Genetically and functionally analyzed in IIH patients and ethnic-matched controls in this study. One heterozygous deletion variant (g.4820_4821del) was identified in one IIH patient, but in none of controls. The variant significantly decreased TBX3 Gene Promoter activities, likely by creating a binding site for sex-determining region Y (SRY), mobility group transcription factor. One heterozygous insertion variant (g.3913_3914ins) was only found in one control, which did not affect TBX3 Gene Promoter activities. Taken together, TBX3 Gene variants may contribute to IIH as a rare risk factor by reducing TBX3 levels.
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two functional sequence variants of the gata6 Gene Promoter in patients with indirect inguinal hernia
Gene, 2014Co-Authors: Yuangang Qiao, Qining Xing, Shuchao Pang, Zhiping Zhang, Wenhui Huang, Bo YanAbstract:Abstract Inguinal hernia is a common surgical disease, majority of which are indirect inguinal hernia (IIH). A positive family history has indicated that Genetic factors play important roles in the IIH development. To date, Genetic causes and underlying mechanisms for inguinal hernia remain largely unknown. During the embryonic development, GATA transcription factor 6 (GATA6) plays an essential role. Mutations in GATA6 Gene and changed GATA6 levels have been associated with human diseases. As GATA6 acts in a dosage-dependent manner, we speculated that changed GATA6 levels, resulting from DNA sequence variants (DSVs) within the Gene regulatory regions, may mediate the IIH development. In this study, the GATA6 Gene Promoter was Genetically and functionally analyzed in IIH patients and ethnic-matched controls. Eleven DNA sequence variants (DSVs), including four SNPs and seven new variants, within the GATA6 Gene Promoter were identified. Two heterozygous DSVs, g.22168361C > A and g.22169106C > T, were identified in two IIH patients, but in none of controls. In cultured human fibroblast, these DSVs significantly reduced the GATA6 Gene Promoter activities. In addition, three heterozygous DSVs were only found in three controls. Five DSVs, including four SNPs and one new variant, were found in both IIH patients and controls with similar frequencies. Therefore, the DSVs within the GATA6 Gene Promoter may contribute to the IIH development as a risk factor by changing the GATA6 levels.
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functional sequence variants within the sirt1 Gene Promoter in indirect inguinal hernia
Gene, 2014Co-Authors: Qingluan Han, Yu Zhang, Hongjin Fan, Qining Xing, Shuchao Pang, Bo YanAbstract:Abstract Inguinal hernia is a common surgical disease, for which Genetic factors have been suggested to play a role. Sirtuin 1 (SIRT1), a highly conserved NAD-dependent class III deacetylase, has been implicated in human diseases. Since SIRT1 regulates differentiation and proliferation of human skeletal muscles and fibroblasts, we speculated that misregulation of SIRT1 Gene, caused by DNA sequence variants (DSVs) within its regulatory regions, may contribute to inguinal hernia development. In this study, SIRT1 Gene Promoter was Genetically and functionally analyzed in patients with indirect inguinal hernia (IIH) (n = 139) and ethnic-matched healthy controls (n = 148). Two heterozygous DSVs, g.69644213G>A and g.69644268T>A, and one single nucleotide polymorphism (SNP), g.69643707A>C (rs35706870), were found in IIH patients, but not in controls. Two closely-linked SNPs, g.69644217A>C (rs932658) and g.69644341G>C (rs2394443), were found in IIH patients with significantly higher frequency, compared to controls (P = 0.006). The C alleles of the SNPs g.69644217A>C (rs932658) and g.69644341G>C (rs2394443) were associated with IIH (P = 0.028, OR 1.600, 95%CI 1.049–2.439). These DSVs significantly altered the transcriptional activities of the SIRT1 Gene Promoter in cultured cells. Therefore, our data suggested that these DSVs may alter the transcriptional activities of SIRT1 Gene Promoter and change SIRT1 levels, contributing to IIH development as risk factors.
Florian Holsboer - One of the best experts on this subject based on the ideXlab platform.
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identification and characterization of a 3 5 cyclic adenosine monophosphate responsive element in the human corticotropin releasing hormone Gene Promoter
Molecular Endocrinology, 1992Co-Authors: Dietmar Spengler, Rainer Rupprecht, L P Van, Florian HolsboerAbstract:The regulation of human corticotropin-releasing hormone (hCRH) Gene Promoter activity by inducers of cAMP was investigated by transient transfection with a construct containing the hCRH Gene Promoter fused to the chloramphenicol acetyltransferase Gene. Expression of hCRH-chloramphenicol acetyltransferase was strongly enhanced by forskolin in the neuroblastoma SK-N-MC and choriocarcinoma JAR cell lines. Overexpression of the catalytic subunit of protein kinase A dispensed the need for forskolin, and cotransfection of cAMP-responsive element-binding protein cDNAs enhanced forskolin-dependent expression of the hCRH Promoter. Progressive 5'-end deletions of the hCRH Promoter delineated a cAMP- responsive region between -226 and -164 base pairs. This fragment contained the sequence TGACGTCA at -221 base pairs, consistent with the consensus motif for a CRE. A homologous oligonucleotide responded to cAMP when cloned in either orientation in front of the thymidine kinase Promoter. However, the level of constitutive and inductive cAMP expression was dependent on the cell line and on intrinsic properties of the Promoter. Mutation of the wild type CRH-CRE sequence into an AP-1 site (TGAGTCA) completely abolished stimulation by cAMP. In contrast, coexpression of the catalytic subunit of protein kinase A dispensed the need for stimulation with forskolin, which showed that the CRH-CRE oligonucleotide served as a functional equivalent of the native CRE element.
Eric B Carstens - One of the best experts on this subject based on the ideXlab platform.
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immediate early baculovirus Genes transactivate the p143 Gene Promoter of autographa californica nuclear polyhedrosis virus
Virology, 1993Co-Authors: Eric B CarstensAbstract:Trans-acting regulatory components of Autographa californica nuclear polyhedrosis virus (AcMNPV) were studied in a transient assay system for their ability to activate the p143 Gene Promoter. A region including 502 nt upstream of the AUG of the p143 Gene was linked to the bacterial chloramphenicol acetyltransferase (CAT) Gene. The p143 Promoter-CAT construct was used to identify AcMNPV immediate-early Gene products required for expression from the p143 Gene early Promoter. Transient expression assays in uninfected Spodoptera frugiperda cells indicated that the IE-1 Gene product was capable of transactivating the p143 Gene Promoter and this activation was augmented by the IE-N Gene product. In addition, another immediate-early Gene, PE-38, was shown to mediate transactivation of the p143 Gene Promoter but not the 39K delayed early Gene Promoter. Deletions to -187 bp relative to the p143 RNA start site did not significantly affect Promoter activity in the combined presence of IE-1 and the HindIII-F fragment. However, a deletion to -52 bp decreased Promoter activity by 40%. In contrast, in the presence of ts8 DNA at 33 degrees, deletions to -52 bp decreased Promoter activity by 80% suggesting that additional viral factors were involved in p143 Gene Promoter regulation.
Sei Sasaki - One of the best experts on this subject based on the ideXlab platform.
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expression of clc kb Gene Promoter in the mouse cochlea
Neuroreport, 2003Co-Authors: Hirofumi Maehara, Shinichi Uchida, Sei Sasaki, Hirooki Okamura, Katsuki Kobayashi, Ken KitamuraAbstract:SUMMARY We have investigated the expression of chloride channels by examining the cochlea of mice harboring the enhanced green fluorescence protein (EGFP) Gene driven by an 11 kbp human CLC-KB Gene Promoter. CLC-KB was seen not only on the stria vascularis but on spiral ligament and limbal fibrocytes, interdental cells and satellite cells of spiral ganglion neurons that are known to possess both Na,K-ATPase and the Na-K-Cl co-transporter (NKCC). These results suggest that some fibrocytes possessing both the CLC-KB and the NKCC may be involved in the regulation of cell volume, transport and recycling of Cl- such as is seen in the stria vascularis. Moreover, these fibrocytes may recycle Cl- through CLC that accompany Na+ and K+ into the cell via NKCC.
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human clc kb Gene Promoter drives the egfp expression in the specific distal nephron segments and inner ear
Journal of The American Society of Nephrology, 2002Co-Authors: Katsuki Kobayashi, Shinichi Uchida, Fumiaki Marumo, Hirooki Okamura, Sei SasakiAbstract:Human CLC-KB has been identified as a kidney-specific member of the CLC chloride channel family, and mutations of the human CLC-KB Gene are known to cause Bartter syndrome type III. A precise understanding of the localization of this channel in the human kidney is imperative to our understanding of the pathophysiology, but this has remained unclear due to the high homology between human CLC-KB and CLC-KA, another kidney-specific member of the same family. The high intraspecies homology also rules out an exact correlation of the human isoforms (CLC-KA and CLC-KB) to the mouse and rat isoforms (CLC-K1 and CLC-K2, respectively). This study created transgenic mice harboring the enhanced green fluorescence protein (EGFP) Gene driven by an 11-kbp human CLC-KB Gene Promoter. Three transgenic lines were Generated, and all of them showed EGFP fluorescence in the kidney, with an identical pattern of localization to the thick ascending limb of Henle's loop, distal tubules, connecting tubules, and intercalated cells of the collecting duct. This localization is exactly the same as that of mouse CLC-K2 identified in a previous report (Kobayashi et al. J Am Soc Neph 12: 1327-1334, 2001). EGFP fluorescence was also detected in the inner ear, more specifically in marginal cells of the stria vascularis and dark cells of the vestibular labyrinth, suggesting that human CLC-KB could play an important role in the fluid transport mechanism of the inner ear. The results (1) confirmed that CLC-KB is the true human homologue of rat and mouse CLC-K2 and (2) established that the 11-kbp human CLC-KB Gene Promoter is sufficient to elicit the precise expression in specific cell types of the kidney and inner ear.
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isolation and characterization of kidney specific clc k2 chloride channel Gene Promoter
Biochemical and Biophysical Research Communications, 1999Co-Authors: Tatemitsu Rai, Shinichi Uchida, Sei Sasaki, Fumiaki MarumoAbstract:CLC-K1 and CLC-K2 are highly homologous kidney-specific chloride channels, but they are expressed in the different nephron segments. To understand the molecular mechanisms of kidney-specific and nephron-segment-specific expression of CLC-K channel Genes, the rat ClC-K2 Gene Promoter was cloned and compared with that of CLC-K1. In the 1.5-kb pair 5'-flanking region of the CLC-K2 Gene, no TATA box was identified around the transcriptional start site, and the proximal region (-32 to -68) was characterized by a GA-rich motif that had a significant sequence similarity to that of the previously isolated CLC-K1 Gene Promoter. In contrast, the distal portion did not have significant sequence similarity to that of CLC-K1. Reporter Gene assay and gel-retardation analysis revealed that the GA-rich motif and the binding of a specific protein(s) to this element were indispensable for the basal Promoter activity of the CLC-K2 Gene. These results suggest that the GA-rich element may have an important role in the Promoter activities of the kidney-specific CLC-K1 and -K2 Genes, but that the GA-element alone is not sufficient for the strict regulation of nephron-segment-specific expression of CLC-K1 and CLC-K2 Genes.
Chawnshang Chang - One of the best experts on this subject based on the ideXlab platform.
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identification of 3 5 cyclic adenosine monophosphate response element and other cis acting elements in the human androgen receptor Gene Promoter
Molecular Endocrinology, 1994Co-Authors: Atsushi Mizokami, Shuyuan Yeh, Chawnshang ChangAbstract:Androgen and androgen receptor (AR) play an important role in sexual differentiation and prostate proliferation. To investigate AR Gene transcriptional regulation, a 2.3-kilobase AR Gene Promoter region was isolated, sequenced, and characterized. Chloramphenicol acetyltransferase (CAT) assay and sequence homology search of AR Gene Promoter among human, rat, and mouse revealed some potential cis-acting elements, including a GC box, a suppressor region, and a purine-rich element. Deletion analysis and gel retardation assay using a 50-base pair (bp) double-strand purine-rich element showed that this purine-rich element can bind to specific proteins in nuclear extract of LNCaP and HeLa cells and may be essential for AR Gene transcription. Furthermore, to investigate the effect of cAMP on AR Gene transcription, we treated LNCaP and HeLa cells with 10 mM (Bu)2cAMP after transfection with CAT Gene reporter plasmids linked to the AR Gene Promoter. This treatment induced several folds of CAT activity in LNCaP cell...
