Shortened microsatellite d(CA)21 sequence down‐regulates promoter activity of matrix metalloproteinase 9 gene

Shimajiri, Shohei; Arima, Nobuyuki; Tanimoto, Akihide; Murata, Y.; Hamada, Tetsuo; Wang, Ke-Yong; Sasaguri, Yasuyuki

doi:10.1016/s0014-5793(99)00863-7

Cited by 188 publications

(153 citation statements)

References 35 publications

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“…Longer (GT)n repeats in the promoter of heme oxygenase-1 gene were associated with lower promoter activity. 37 In contrast, Shimajiri et al 48 showed that longer (CA)n repeats in the matrix metalloproteinase 9 promoter enhanced activity. We have found that shorter (np16) GT repeats in intron II of the human TLR2 gene were significantly associated with the presence of TB in this Korean population.…”

Section: Discussionmentioning

confidence: 95%

The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans

et al. 2006

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The observation that Toll-like receptor (TLR)2-deficient mice are highly susceptible to mycobacteria suggests that mutations altering TLR2 expression may impair host response to Mycobacterium tuberculosis. We evaluated the association between guanine-thymine (GT) repeat polymorphism in intron II of the TLR2 gene and the presence of tuberculosis (TB) in Koreans. The numbers of GT repeats were determined by PCR and gene scans for 176 TB patients and 196 controls. The recombinant TLR2 promoter/exonI/exonII/intronII/luciferase constructs including three representative repeats: (GT) 13 , (GT) 20 , and (GT) 24 were transfected into K562 cells, and luciferase activities were estimated and compared. The expression of TLR2 on CD14 þ peripheral blood mononuclear cells (PBMC) from healthy volunteers were measured with flow cytometry. Genotypes with shorter GT repeats were more common among TB patients (49.4 vs 37.7%, P ¼ 0.02). This observation was confirmed among 82 other TB patients as a validation cohort. Shorter GT repeats were associated with weaker promoter activities and lower TLR2 expression on CD14 þ PBMCs. In conclusion, the development of TB disease in Koreans was associated with shorter GT repeats in intron II of the TLR2 gene. This association is correlated with lower expression of TLR2 through weaker promoter activity for genes with shorter GT repeats. Genes and Immunity (2006) 7, 150-155.

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Section: Discussionmentioning

confidence: 95%

The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans

et al. 2006

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“…Polymorphic dinucleotide microsatellites in or near promoters have been identified and found to regulate many other genes (Borrmann et al, 2003;Gebhardt et al, 1999;Shimajiri et al, 1999;Wang et al, 2005). One of the microsatellites that consists of GA repeats is highly conserved from mouse to human and is therefore likely to have human relevance.…”

Section: Discussionmentioning

confidence: 99%

Ets factors and a newly identified polymorphism regulate Fli1 promoter activity in lymphocytes

Nowling¹,

Fulton²,

Chike-Harris³

et al. 2008

Molecular Immunology

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Fli1 is an Ets family member that is essential for embryonic development. Increasing evidence suggests modulating Fli1 gene expression impacts lymphocyte development/function and is an important mediator in the autoimmune disease lupus. Fli1 is over-expressed in splenic lymphocytes in lupus prone mouse strains and in PBMCs of lupus patients. Presently, it is unknown how Fli1 gene expression is controlled in lymphocytes or how it becomes over-expressed in lupus. Therefore, we examined Fli1 regulation in a murine B cell line and T cell line and identified several cis-regulatory elements within a 230 bp region that contribute to Fli1 promoter activity. Ets factors Elf1, Tel and Fli1 bind in vitro to this region and increase endogenous Fli1 expression when over-expressed in a T cell line. In addition, we determined that a microsatellite located adjacent to the region containing these cis-regulatory elements is polymorphic in three lupus prone mouse strains and that the length of the microsatellite is inversely correlated with promoter activity in a T cell line. These results suggest that several Ets factors, including Fli1 itself, are involved in the transcriptional regulation of Fli1 in lymphocytes. Furthermore, the presence of a polymorphic microsatellite in the Fli1 promoter may contribute to increased Fli1 expression in T cells during lupus disease progression.

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“…[39][40][41][42][43] The number of tandem repeats has been shown to influence the transcription rate either by a direct interaction with a transcription factor 44,45 or by affecting spacing between flanking regions. 46 Considering the data of the present paper it is tempting to speculate that a long IL10.G allele might be responsible for a high IL10 production, a typical aspect of SLE pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

et al. 2002

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Many lines of evidence suggest that IL10 is a strong candidate gene for systemic lupus erythematosus (SLE) susceptibility. In our previously reported study an allele (IL10.G-140bp) of the microsatellite IL10.G located at position À1100 was significantly increased in Italian SLE patients in comparison with controls. Starting from this observation, we tested if sequence variations in the vicinity of IL10.G were more strongly associated with SLE. We performed a comprehensive association study including 26 SNPs (of which four were newly identified in the present study by DHPLC analysis) spanning 8.5 Kb of the 5 0 flanking and the transcribed region of the IL10 gene. The association study was performed by the DNA pool method on an extended panel of Italian patients (205) and controls (631). Haplotypic associations were studied by individual typing of seven selected markers surrounding IL10.G. Gene, genotype and haplotype frequencies were not significantly different in patients and controls. Thus the IL10.G microsatellite remains to date the only IL10 marker associated with SLE in our population. A meta-analysis of all published results indicates a possible direct role of the IL10.G repeat number in SLE susceptibiliy.

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Shortened microsatellite d(CA)21 sequence down‐regulates promoter activity of matrix metalloproteinase 9 gene

Cited by 188 publications

References 35 publications

The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans

The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans

Ets factors and a newly identified polymorphism regulate Fli1 promoter activity in lymphocytes

Association tests with systemic lupus erythematosus (SLE) of IL10 markers indicate a direct involvement of a CA repeat in the 5′ regulatory region

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