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

Béatrice Horard 1 Angéline Eymery 2 Geneviève Fourel 1 Nikita Vassetzky 3 Jacques Puechberty 4 Gérard Roizes 4 Kevin Lebrigand 5 Pascal Barbry 5 Aurélie Laugraud 6 Christian Gautier 7, 8 Elsa Ben Simon 1 Frédéric Devaux 9 Frédérique Magdinier 1 Claire Vourc'H 2 Eric Gilson 1
1 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
2 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
3 ISTC - Engelhardt Institute of Molecular Biology
4 IGH - Institut de génétique humaine
5 IPMC - Institut de pharmacologie moléculaire et cellulaire
6 LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
7 BAMBOO - An algorithmic view on genomes, cells, and environments
Inria Grenoble - Rhône-Alpes, LBBE - Laboratoire de Biométrie et Biologie Evolutive - UMR 5558
8 Baobab
PEGASE - Département PEGASE [LBBE]
9 LGM - Génomique des Microorganismes
Abstract : 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 the first valuable tool for systematic and genome-wide analyses of the methylation and transcriptional status of the repetitive counterpart of the human genome.
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Béatrice Horard, Angéline Eymery, Geneviève Fourel, Nikita Vassetzky, Jacques Puechberty, et al.. Global analysis of DNA methylation and transcription of human repetitive sequences.. Epigenetics, Taylor & Francis, 2009, 4 (5), pp.339-50. ⟨hal-00851248⟩

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