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http://hdl.handle.net/10662/7274
Títulos: | Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor |
Autores/as: | Morales Hernández, Antonio González Rico, Francisco Javier Román García, Ángel Carlos Rico Leo, Eva María Álvarez Barrientos, Alberto Sánchez Ruiz, Laura Macia Ortega, Ángela Rodríguez Heras, Sara García Pérez, José Luis Merino Fernández, Jaime María Fernández Salguero, Pedro María |
Palabras clave: | Diferenciación celular;Regulación de genes;Células de carcinoma;Elementos discretos de Alu;Cell differentiation;Gene regulation;Carcinoma cells;Discrete Alu elements |
Fecha de publicación: | 2016 |
Resumen: | Cell differentiation is a central process in development and in cancer growth and dissemination. OCT4 (POU5F1) and NANOG are essential for cell stemness and pluripotency; yet, the mechanisms that regulate their expression remain largely unknown. Repetitive elements account for almost half of the Human Genome; still, their role in gene regulation is poorly understood. Here, we show that the dioxin receptor (AHR) leads to differentiation of human carcinoma cells through the transcriptional upregulation of Alu retrotransposons, whose RNA transcripts can repress pluripotency genes. Despite the genome-wide presence of Alu elements, we provide evidences that those located at the NANOG and OCT4 promoters bind AHR, are transcribed by RNA polymerase-III and repress NANOG and OCT4 in differentiated cells. OCT4 and NANOG repression likely involves processing of Alu-derived transcripts through the miRNA machinery involving the Microprocessor and RISC. Consistently, stable AHR knockdown led to basal undifferentiation, impaired Alus transcription and blockade of OCT4 and NANOG repression. We suggest that transcripts produced from AHR-regulated Alu retrotransposons may control the expression of stemness genes OCT4 and NANOG during differentiation of carcinoma cells. The control of discrete Alu elements by specific transcription factors may have a dynamic role in genome regulation under physiological and diseased conditions. |
URI: | http://hdl.handle.net/10662/7274 |
ISSN: | 0305-1048 |
DOI: | 10.1093/nar/gkw095 |
Colección: | DBYBM - Artículos |
Archivos
Archivo | Descripción | Tamaño | Formato | |
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nar_gkw095.pdf | 6,16 MB | Adobe PDF | Descargar |
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