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REGULACIÓN TRANSCRIPCIONAL DE LA EXPRESIÓN DE LA NAD QUINASA DE Giardia duodenalis: UNA APROXIMACIÓN in silico
Transcriptional Regulation of Giardia duodenalis NAD Kinase Expression: an In Silico Approach
DOI:
https://doi.org/10.15446/abc.v29n3.96554Palabras clave:
expresión génica, metabolismo energético, reguladores transcripcionales (es)energy metabolism, gene expression, transcriptional regulatory elements (en)
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Giardia duodenalis es un protozoario parásito de gran importancia en salud pública, ya que causa la enfermedad gastrointestinal más prevalente del mundo, la giardiasis. El tratamiento farmacológico para esta parasitosis consiste en la administración de nitroimidazoles y benzimidazoles, sin embargo, se han detectado resistencia al tratamiento y múltiples efectos secundarios. Por tal razón, en estudios anteriores se postuló a la NAD quinasa de G. duodenalis (glnadk), como posible blanco farmacológico. En este trabajo, se realizó una aproximación bioinformática de los mecanismos de regulación transcripcional de este gen. Para la regulación en cis, se partió de la búsqueda de elementos conservados en otros genes del parásito y, mediante el uso de los servidores MEME y Tomtom, se buscaron nuevos motivos y sitios de unión a factores de transcripción. Para la identificación de elementos reguladores trans con sitio de unión al promotor de glnadk, se empleó el servidor PROMO y, para la identificación de genes candidato a factor de transcripción en el genoma de G. duodenalis, alineamientos múltiples de secuencia. Se identificaron elementos reguladores en cis conservados, y nuevos motivos de unión a proteínas reguladoras en el promotor de glnadk. Adicionalmente, se identificaron posibles factores de transcripción que podrían participar en la regulación de glnadk, y se postularon genes candidato que codificarían para estos elementos reguladores.
Giardia duodenalis is a protozoan parasite of great public health importance, since it causes the most prevalent gastrointestinal disease in the world, giardiasis. Pharmacological treatment for this parasitosis consists of the administration of nitroimidazoles and benzimidazoles, however, resistance to treatment and multiple side effects have been detected. For this reason, in previous studies, G. duodenalis NAD kinase (glnadk) was postulated as a possible drug target. In this work, a bioinformatic approach to the transcriptional regulation mechanisms of this gene was carried out. For the cis regulation, we started from the search for conserved elements in other genes of the parasite and, through the use of the MEME and Tomtom servers, new motifs and binding sites for transcription factors were explored. For the scanning of trans regulatory elements with binding site to the glnadk promoter, the PROMO server was used, and, for the identification of candidate genes for a transcription factor in the G. duodenalis genome, multiple sequence alignments. Conserved cis regulatory elements and new regulatory protein binding motifs in the glnadk promoter were identified. Additionally, possible transcription factors that could participate in the regulation of glnadk were identified, and candidate genes that would code for these regulatory elements were postulated.
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