Nucleic Acids Research Advance Access originally published online on August 31, 2009
Nucleic Acids Research 2009 37(19):6340-6354; doi:10.1093/nar/gkp639
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Nucleic Acids Research, 2009, Vol. 37, No. 19 6340-6354
© The Author(s) 2009. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Gene Regulation, Chromatin and Epigenetics |
A transcriptomic analysis of human centromeric and pericentric sequences in normal and tumor cells
1INSERM, U823, Université Joseph Fourier, Institut Albert Bonniot, La Tronche F-38706, Grenoble, 2Laboratoire de Biologie Moléculaire de la Cellule, UMR 5239, CNRS, ENS-LYON, Université LYON 1/HCL, 165, Chemin du Grand Revoyet, 69495 Pierre Bénite, 3INSERM, U836, Université Joseph Fourier, Institut de Neurosciences, La Tronche, F-38700, Grenoble and 4CHU de Grenoble, La Tronche F-38706
*To whom correspondence should be addressed. Tel: +33 4 76 54 94 70; Fax: +33 4 76 54 95 95; Email: claire.vourch{at}ujf-grenoble.fr
Received March 16, 2009. Revised July 16, 2009. Accepted July 17, 2009.
Although there is now evidence that the expression of centromeric (CT) and pericentric (PCT) sequences are key players in major genomic functions, their transcriptional status in human cells is still poorly known. The main reason for this lack of data is the complexity and high level of polymorphism of these repeated sequences, which hampers straightforward analyses by available transcriptomic approaches. Here a transcriptomic macro-array dedicated to the analysis of CT and PCT expression is developed and validated in heat-shocked (HS) HeLa cells. For the first time, the expression status of CT and PCT sequences is analyzed in a series of normal and cancer human cells and tissues demonstrating that they are repressed in all normal tissues except in the testis, where PCT transcripts are found. Moreover, PCT sequences are specifically expressed in HS cells in a Heat-Shock Factor 1 (HSF1)-dependent fashion, and we show here that another independent pathway, involving DNA hypo-methylation, can also trigger their expression. Interestingly, CT and PCT were found illegitimately expressed in somatic cancer samples, whereas PCT were repressed in testis cancer, suggesting that the expression of CT and PCT sequences may represent a good indicator of epigenetic deregulations occurring in response to environmental changes or in cell transformation.