TATA box polymorphisms in human gene promoters and associated hereditary pathologies

Савинкова, Л. К.; Пономаренко, М. П.; Пономаренко, П. М.; Драчкова, И. А.; Лысова, М. В.; Arshinova, Tatyana; Колчанов, Н. А.

doi:10.1134/s0006297909020011

Cited by 51 publications

(38 citation statements)

References 136 publications

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“…Chst12 and Grifin reside in an 86 kb region (chr12: chr12:14,541,567-14,627,442 bp) that was unique to the hypertensive SS strain compared to normotensive BN, SR, and WKY strains (Figure 3). Within this region, 4 variants unique to the SS altered binding sites in the proximal Chst12 regulatory regions for multiple TF have been previously implicated in the pathogenesis of hypertension (e.g., NF- k B, 31, 32 Sp1, 33-35 and TBP 36 ).…”

Section: Discussionmentioning

confidence: 99%

Refined Mapping of a Hypertension Susceptibility Locus on Rat Chromosome 12

et al. 2014

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Previously, we found that transferring 6.1 Mb of SS chromosome 12 (13.4-19.5 Mb) onto the consomic SS-12BN background significantly elevated mean arterial pressure in response to an 8% NaCl diet (178±7 vs. 144±2 mmHg; P<0.001). Using congenic mapping, we have now narrowed the blood pressure locus by 86% from a 6.1 Mb region containing 133 genes to an 830 kb region (chr12:14.36-15.19 Mb) with 14 genes. Compared with the SS-12BN consomic, the 830 kb blood pressure locus was associated with a Δ+15 mmHg (P<0.01) increase in blood pressure, which coincided with elevated albuminuria (Δ+32 mg/day; P<0.001), proteinuria (Δ+48 mg/day; P<0.01), protein casting (Δ+154%; P<0.05), and renal fibrosis (Δ+79%; P<0.05). Of the 14 genes residing in the 830 kb locus, 8 were differentially expressed and among these, Chst12 (carbohydrate chondroitin 4 sulfotransferase 12) was the most consistently down-regulated by 2.6 to 4.5-fold (P<0.05) in both the renal medulla and cortex under normotensive and hypertensive conditions. Moreover, whole genome sequence analysis of overlapping blood pressure loci revealed an ∼86 kb region (chr12:14,541,567-14,627,442 bp) containing single nucleotide variants near Chst12 that are unique to the hypertensive SS strain when compared to the normotensive BN, SR, and WKY strains. Finally, the 830 kb interval is syntenic to a region on human chromosome 7 that has been genetically linked to blood pressure, suggesting that insight gained from our SS-12BN congenic strain may be translated to a better understanding of human hypertension.

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Section: Discussionmentioning

confidence: 99%

Refined Mapping of a Hypertension Susceptibility Locus on Rat Chromosome 12

et al. 2014

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“…Our approach to identifying this motif was based on an observation of a human mutation. A compendium of human mutations that reveal functional sites within core promoters, such as single nucleotide substitutions in thalassemias, confirms that analyses of these types of mutations have been useful for defining novel instances of promoter motifs (43). …”

Section: Discussionmentioning

confidence: 82%

Genome-wide detection of a TFIID localization element from an initial human disease mutation

Yang

Laflamme

Gotea

et al. 2010

Nucleic Acids Research

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Eukaryotic core promoters are often characterized by the presence of consensus motifs such as the TATA box or initiator elements, which attract and direct the transcriptional machinery to the transcription start site. However, many human promoters have none of the known core promoter motifs, suggesting that undiscovered promoter motifs exist in the genome. We previously identified a mutation in the human Ankyrin-1 (ANK-1) promoter that causes the disease ankyrin-deficient Hereditary Spherocytosis (HS). Although the ANK-1 promoter is CpG rich, no discernable basal promoter elements had been identified. We showed that the HS mutation disrupted the binding of the transcription factor TFIID, the major component of the pre-initiation complex. We hypothesized that the mutation identified a candidate promoter element with a more widespread role in gene regulation. We examined 17 181 human promoters for the experimentally validated binding site, called the TFIID localization sequence (DLS) and found three times as many promoters containing DLS than TATA motifs. Mutational analyses of DLS sequences confirmed their functional significance, as did the addition of a DLS site to a minimal Sp1 promoter. Our results demonstrate that novel promoter elements can be identified on a genome-wide scale through observations of regulatory disruptions that cause human disease.

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“…Despite this variability in the TATA boxes, some TATA containing promoters may be very sensitive to mutations in TATA boxes. This is confirmed by molecular genetically and clini cally identified single nucleotide polymorphisms (SNP) of TATA boxes in human gene promoters asso ciated with predisposition to hereditary diseases (Savinkova et al, 2009). …”

Section: Introductionmentioning

confidence: 78%

Change of TATA-binding protein affinity to oligonucleotides corresponding to TATA boxes in human gene promoters bearing polymorphisms associated with hereditary diseases

Драчкова

Arshinova

Пономаренко

et al. 2012

Russ J Genet Appl Res

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Single nucleotide polymorphisms (SNPs) in the regulatory regions of human genes and, in par ticular, TATA boxes can alter the sensitivity to bacterial and viral infections and to drugs used for their treat ment. These SNPs are associated with the risk of widespread multifactorial human diseases, such as arthritis, hypertension, cancer, Alzheimer's disease, and others. Interaction of the TATA binding protein (TBP) with TATA boxes on TATA containing promoters nucleates the preinitiation complex assemblage, which is the initial stage of transcription regulation. This study considers the change of TBP affinity to the TATA boxes of human MBL, CYP 2A6, SOD1, and TPI genes bearing SNPs associated with autoimmune diseases, cardio vascular diseases, amyotrophic lateral sclerosis, neurodegenerative disorders, hypersensitivity to bacterial infections, etc. In all cases a decrease in the affinity of TBP to TATA containing oligonucleotides was shown.

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TATA box polymorphisms in human gene promoters and associated hereditary pathologies

Cited by 51 publications

References 136 publications

Refined Mapping of a Hypertension Susceptibility Locus on Rat Chromosome 12

Refined Mapping of a Hypertension Susceptibility Locus on Rat Chromosome 12

Genome-wide detection of a TFIID localization element from an initial human disease mutation

Change of TATA-binding protein affinity to oligonucleotides corresponding to TATA boxes in human gene promoters bearing polymorphisms associated with hereditary diseases

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