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Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects. Since RAAS over activity contributes to hypertension in obesity, we have made transgenic mice (TG) containing either Hap I or Hap II of the hAGT gene to understand the role of obesity on its transcriptional regulation. Although, a high-fat diet (60% Kcal from fat, 12 weeks) elevates hAGT and mAGT regardless of haplotype, this effect is significantly (p<0.05) accentuated in Hap I mice, in both adipose and liver tissues. Chromatin Immuno- precipitation (ChIP) assay shows an increased binding of transcription factors including, GR, CEBPβ and STAT3 to the chromatin of the Hap I TG mice after high-fat diet as compared to Hap II TG mice (p<0.05). Differential plasma levels of hAGT in Hap II and I mice, after high-fat diet, further corroborate the variable transcriptional regulation of the hAGT, governed by gene-haplotypes. Taken together, our results show that SNPs in the Hap-I of the hAGT gene promote high-fat diet-induced binding of transcription factors GR, CEBP-β and STAT3, which lead to elevated expression of the hAGT gene in hepatic and adipose tissues.
Pubmed ID: 28467442 RIS Download
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In an effort to strongly support the collaborative nature of scientific research, BIOBASE offers access to their tools. Programs that are available through this portal are: * AliBaba 2.1: AliBaba2 is a program for predicting binding sites of transcription factor binding sites in an unknown DNA sequence. Therefore it uses the binding sites collected in TRANSFAC. AliBaba2 is currently the most specific tool for predicting sites. * Boxshade 3.3.1: Pretty Printing and Shading of Multiple-Alignment files. * ClustalW 1.8: ClustalW Multiple Sequence Alignment Program. * Dialign2.0: Multiple Sequence Alignment Program. * F-Match 1.0: F-MATCH is a program for identifying statistically overrepresented Transcription Factor Binding Sites (TFBS) in a set of sequences compared against a control set, assuming a binomial distribution of TFBS frequency. The program reads MATCH output files for the query and control sets. F-Match uses a library of mononucleotide weight matrices from TRANSFAC 6.0 * Match 1.0 Public: Match is designed for searching potential binding sites for transcription factors (TF binding sites) nucleotide sequences. MatchTM uses a library of mononucleotide weight matrices from TRANSFAC 6.0 * molwSearch 1.0: Search for transcription factors with a certain molecular weight. * P-Match 1.0: P-Match is a new tool for identifying transcription factor binding sites (TF binding sites) in DNA sequences. It combines pattern matching and weight matrix approaches thus providing higher accuracy of recognition than each of the methods alone. P-Match uses a library of mononucleotide weight matrices from TRANSFAC 6.0 along with the site alignments associated with these matrices. * Patch 1.0: Search for potential transcription factor binding sites in your own sequences with the pattern search program using TRANSFAC 6.0 public sites. * m2transfac 1.0: m2transfac is a PWM-PWM alignment interface for the TRANSFAC(R) database. For given user motifs, m2transfac reports all non-overlapping pairwise alignments to a TRANSFAC(R) matrix which satisfy a specified threshold. * MatrixCatch 2.7: The MatrixCatch tool is designed for searching potential composite elements (CEs) for transcription factors (TFs) in any DNA sequence, which may be of interest. MatrixCatch uses a library of CE matrix models, which were compiled on a basis of experimentally identified CEs collected in TRANSCOMPEL database and mononucleotide weight matrices for single TF-binding sites collected in TRANSFAC 6.0 public database. * Composite Module Analyst (CMA) 1.0: CMA reads output of Match program and applies a genetic algorithm in order to define promoter models based on the composition of transcription factor binding sites and their pairs. * PolyA Scan 0.000707: Scanning a Sequence for potential Polyadenylation Sites. * ReadSeq 2.0: ReadSeq reads and writes nucleic/protein sequences in various formats. * SignalScan: Analysis of DNA Sequences for known Eukaryotic Signals * SbBlast 1.0: Search Tool for Sequence Search in the S/MARt Binder Database. SbBlast makes use of the BLAST Sequence Similarity Search Tool - Version 2.0.13 (May-26-2000). * SnpFind 0.3: SNPFIND is a tool for searches in the Database of Single Nucleotide Polymorphisms. The search algorithm used for the database search is the BLAST algorithm. * TfBlast 0.1: Search Tool for Sequence Search in the TRANSFAC Factor Table. SbBlast makes use of the BLAST Sequence Similarity Search Tool - Version 2.0.13 (May-26-2000).
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