Hitchhiking Trypanosoma cruzi minicircle DNA affects gene expression in human host cells via LINE-1 retrotransposon
Mem. Inst. Oswaldo Cruz
;
101(8): 833-843, Dec. 2006. ilus
Artigo
em Inglês
| LILACS
| ID: lil-440569
ABSTRACT
The horizontal transfer of Trypanosoma cruzi mitochondrial minicircle DNA to the genomes of naturally infected humans may play an important role in the pathogenesis of Chagas disease. Minicircle integrations within LINE-1 elements create the potential for foreign DNA mobility within the host genome via the machinery associated with this retrotransposon. Here we document integration of minicircle DNA fragments in clonal human macrophage cell lines and their mobilization over time. The movement of an integration event in a clonal transfected cell line was tracked at three months and three years post-infection. The minicircle sequence integrated into a LINE-1 retrotransposon; one such foreign fragment subsequently relocated to another genomic location in association with associated LINE-1 elements. The p15 locus was altered at three years as a direct effect of minicircle/LINE-1 acquisition, resulting in elimination of p15 mRNA. Here we show for the first time a molecular pathology stemming from mobilization of a kDNA/LINE-1 mutation. These genomic changes and detected transcript variations are consistent with our hypothesis that minicircle integration is a causal component of parasite-independent, autoimmune-driven lesions seen in the heart and other target tissues associated with Chagas disease.
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Assunto principal:
Trypanosoma cruzi
/
Expressão Gênica
/
DNA de Cinetoplasto
/
Retroelementos
/
Elementos Nucleotídeos Longos e Dispersos
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Mem. Inst. Oswaldo Cruz
Assunto da revista:
Medicina Tropical
/
Parasitologia
Ano de publicação:
2006
Tipo de documento:
Artigo
País de afiliação:
Brasil
/
Estados Unidos
Instituição/País de afiliação:
Universidade de Brasília/BR
/
University of California/US
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