@misc{10481/88512,
year = {2016},
url = {https://hdl.handle.net/10481/88512},
abstract = {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.},
organization = {Ministerio de Economía y Competitividad [BFU2011- 22678, SAF2014-51813-R to P.M.F-S.]; Junta de Extremadura [GR10008, GR15008]; Red Temática de Investigación Cooperativa en Cáncer (RTICC); Carlos III Institute; Spanish Ministry of Economy and Competitiveness [RD12/0036/0032]; FPI Fellowship from the Junta de Extremadura (to A.M.H.); Marie Curie IRG project (FP7-PEOPLE-2007-4-3-IRG: SOMATIC LINE-1, in part to A.M.); CICE-FEDER-P09-CTS-4980, CICE-FEDERP12- CTS-2256, Plan Nacional de I+D+I 2008–2011 and 2013–2016 (FIS-FEDER-PI11/01489, FIS-FEDERPI14/ 02152), PCIN-2014-115-ERA-NET NEURON II (to J.L.G.P.); European Research Council [ERC-Consolidator ERC-STG-2012-233764]; International Early Career Scientist grant from the Howard Hughes Medical Institute [IECS-55007420]; European Union FEDER program. Funding for open access charge: Ministerio de Economía y Competitividad [BFU2011-22678, SAF2014-51813-R to P.M.F-S.].},
publisher = {Oxford University Press},
title = {Alu retrotransposons promote differentiation of human carcinoma cells through the aryl hydrocarbon receptor},
doi = {10.1093/nar/gkw095},
author = {Morales-Hernández, Antonio and Rodríguez Heras, Sara and García Pérez, José Luis},
}