Genetic inactivation of ATRX leads to a decrease in the amount of telomeric cohesin and of telomere transcription in human glioma cells
(2015) Molecular and Cellular Biology — Vol. 35, n° 16, p. 2818-2830 (2015)
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- Mutations in ATRX, a chromatin remodeling protein, are associated with the telomerase-independent ALT pathway of telomere maintenance in several types of cancer, including human gliomas. In telomerase-positive glioma cells, we found that by immunofluorescence ATRX localized not far from the chromosome ends but not exactly at the telomere termini. Chromatin immunoprecipitation (ChIP) experiments confirmed a subtelomeric localization for ATRX. Yet, shRNA-mediated genetic inactivation of ATRX failed to trigger the ALT pathway. Cohesin has been recently shown to be part of telomeric chromatin. Here, using ChIP, we showed that genetic inactivation of ATRX provoked a diminution in the amount of cohesin in subtelomeric regions of telomerase-positive glioma cells. Inactivation of ATRX also led to a diminution in the amount of TERRAs, non coding RNAs resulting from transcription of telomeric DNA, as well as to a decrease in RNAPII levels at the telomeres. Our data suggest that ATRX might establish functional interactions with cohesin on telomeric chromatin in order to control TERRA levels and that one or the other or both of these events might be relevant to the triggering of the ALT pathway in cancer cells that exhibit genetic inactivation of ATRX.
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Eid, R., Demattei, M.-V., Episkopou, C., Augé-Gouillou, C., Decottignies, A., Grandin, N., & Charbonneau, M. (2015). Genetic inactivation of ATRX leads to a decrease in the amount of telomeric cohesin and of telomere transcription in human glioma cells. Molecular and Cellular Biology, 35(16), 2818-2830. https://doi.org/10.1128/MCB.01317-14 (Original work published 2015)