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Transcriptional activity of the RHOB gene is influenced by regulatory polymorphisms in its promoter region.

ABSTRACT: Osteoarthritis (OA) is a chronic joint disease with genetic as well as environmental factors contributing to its etiology. We recently identified RHOB as a gene overexpressed in osteoarthritis. Interestingly, RHOB harbors numerous polymorphisms in its promoter region and genotyping of OA patients and healthy controls revealed an association of the single nucleotide polymorphism (SNP) rs585017 with the disease. We here set out to investigate the influence of RHOB promoter polymorphisms on the transcriptional activity of the gene and we found evidence that the SNPs rs2602160 and rs585017 cooperate in regulating RHOB expression. In addition, a variable number of tandem repeats (VNTR) impacts on the RHOB transcriptional activity in a cell type restricted manner. These results mechanistically link our previous finding of an elevated RHOB expression to the disease associated SNP rs585017 and confirm a role for regulatory polymorphisms in osteoarthritis.

SUBMITTER: Mahr S

PROVIDER: S-EPMC2269035 | biostudies-literature | 2007

REPOSITORIES: biostudies-literature

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Transcriptional activity of the RHOB gene is influenced by regulatory polymorphisms in its promoter region.

Mahr Sandra S Müller-Hilke Brigitte B

Genomic medicine 20071120 3-4

Osteoarthritis (OA) is a chronic joint disease with genetic as well as environmental factors contributing to its etiology. We recently identified RHOB as a gene overexpressed in osteoarthritis. Interestingly, RHOB harbors numerous polymorphisms in its promoter region and genotyping of OA patients and healthy controls revealed an association of the single nucleotide polymorphism (SNP) rs585017 with the disease. We here set out to investigate the influence of RHOB promoter polymorphisms on the tra ...[more]

PMID: 18923937

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Project description:BackgroundSuccess of meat production and selection for improvement of meat quality is among the primary aims in animal production. Meat quality traits are economically important in swine; however, the underlying genetic nature is very complex. Therefore, an improved pork production strongly depends on identifying and studying how genetic variations contribute to modulate gene expression. Promoters are key regions in gene modulation as they harbour several binding motifs to transcription regulatory factors. Therefore, polymorphisms in these regions are likely to deeply affect RNA levels and consequently protein synthesis. In this study, we report the identification of single nucleotide polymorphisms (SNPs) in promoter regions of candidate genes involved in development, cellular differentiation and muscle growth in Sus scrofa. We identified SNPs in the promoter regions of genes belonging to the Myogenic Regulatory Factors (MRF) gene family (the Myogenic Differentiation gene, MYOD1) and to Growth and Differentiation Factors (GDF) gene family (Myostatin gene, MSTN, GDF8), in Casertana and Large White breeds. The purpose of this study was to investigate if polymorphisms in the promoters could affect the transcriptional activity of these genes. With this aim, we evaluated in vitro the functional activity of the luciferase reporter gene luc2 activity, driven by two constructs carrying different promoter haplotypes.ResultsWe tested the effects of the G302A (U12574) transition on the promoter efficiency in MYOD1 gene. We ascertained a difference in transcription efficiency for the two variants. A stronger activity of the A-carrying construct is more evident in C2C12. The luciferase expression driven by the MYOD1-A allelic variant displayed a 3.8-fold increased transcriptional activity. We investigated the activity of two haplotype variants (AY527152) in the promoter of GDF8 gene. The haploptype-1 (A435-A447-A879) up-regulated the expression of the reporter gene by a two-fold increase, and hence presumably of the GDF8 gene, in both CHO and C2C12 cultured cells.ConclusionsIn vitro the MYOD1-A allelic variant could up-regulate the expression of MYOD1 gene. Additionally, we could assess a different response of in vitro gene expression according to cell type used to transfect constructs, suggesting that MyoD activation is regulated by mechanisms that are specific of myoblasts.

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Transcriptional activity of the RHOB gene is influenced by regulatory polymorphisms in its promoter region.

Publications

Transcriptional activity of the RHOB gene is influenced by regulatory polymorphisms in its promoter region.

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