Global analysis of DNA methylation and transcription of human repetitive sequences.
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.
Horard
Béatrice
B
Laboratoire de Biologie Moléculaire de la Cellule UMR CNRS 5239, ENS Lyon, Université LYON 1, HCL, Lyon, France. bhorard@ens-lyon.fr
Eymery
Angéline
A
Fourel
Geneviève
G
Vassetzky
Nikita
N
Puechberty
Jacques
J
Roizes
Gérard
G
Lebrigand
Kevin
K
Barbry
Pascal
P
Laugraud
Aurélie
A
Gautier
Christian
C
Simon
Elsa Ben
EB
Devaux
Frédéric
F
Magdinier
Frédérique
F
Vourc'h
Claire
C
Gilson
Eric
E
D001374:Azacitidine / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects; D015342:DNA Probes / Q000378:metabolism; D020869:Gene Expression Profiling; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D015203:Reproducibility of Results; D014158:Transcription, Genetic / Q000187:drug effects
D015342:DNA Probes; D012333:RNA, Messenger; D001374:Azacitidine