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Research Paper

Global analysis of DNA methylation and transcription of human repetitive sequences.

Béatrice Horard, Angéline Eymery, Genevieve Fourel, Nikita Vassetzky, Jacques Puechberty, Gerard Roizes, Kevin Lebrigand, Pascal Barbry, Aurélie Laugraud, Christian Gautier, Elsa Ben Simon, Frédéric Devaux, Frédérique Magdinier, Claire Vourc’h and Eric Gilson

Half of the human genome consists of repetitive DNA sequences. Recent studies in various organisms highlight the role of chromatin regulation of repetitive DNA in gene regulation as well as in maintainance of chromosomes and genome integrity. Hence, repetitive DNA sequences might be potential “sensors” for chromatin changes associated with pathogenesis. Therefore, we developed a new genomic tool called RepArray. RepArray is a repeat-specific microarray composed of a representative set of human repeated sequences including transposon-derived repeats, simple sequences repeats, tandemly repeated sequences such as centromeres and telomeres. We showed that combined to anti-methylcytosine immunoprecipitation assay, the RepArray can be used to generate repeat-specific methylation maps. Using cell lines impaired chemically or genetically for DNA methyltransferases activities, we were able to distinguish different epigenomes demonstrating that repeats can be used as markers of genome-wide methylation changes. Besides, using a well-documented system model, the thermal stress, we demonstrated that RepArray is also a fast and reliable tool to obtain an overview of overall transcriptional activity on whole repetitive compartment in a given cell type. Thus, the RepArray represents thus the first valuable tool for systematic and genome-wide analyses of the methylation and transcriptional status of the repetitive counterpart of the human genome.

Authors

Béatrice Horard Corresponding author: bhorard@ens-lyon.fr

Université LYON 1

Angéline Eymery

Université Joseph Fourier

Genevieve Fourel

Université LYON 1

Nikita Vassetzky

Russian Academy of Sciences

Jacques Puechberty

Institut de Génétique Humaine

Gerard Roizes

Institut de Génétique Humaine

Kevin Lebrigand

Institut de Pharmacologie Moléculaire et Cellulaire, CNRS; Université de Nice Sophia Antipolis

Pascal Barbry

Institut de Pharmacologie Moléculaire et Cellulaire, CNRS; Université de Nice Sophia Antipolis

Aurélie Laugraud

PRABI/ Laboratoire de Biométrie et Biologie Evolutive ; UNIV LYON1- CNRS

Christian Gautier

PRABI/ Laboratoire de Biométrie et Biologie Evolutive ; UNIV LYON1- CNRS

Elsa Ben Simon

Université LYON 1

Frédéric Devaux

Laboratoire de Genetique Moleculaire - CNRS UMR 8541

Frédérique Magdinier

Université LYON 1

Claire Vourc’h

Université Joseph Fourier

Eric Gilson Corresponding author: egilson@ens-lyon.fr

Université LYON 1