title: Research resource: genome-wide profiling of methylated promoters in endometriosis reveals a subtelomeric location of hypermethylation.
abstract: Several lines of evidence indicate that endometriosis could be partially due to selective epigenetic deregulations. Promoter hypermethylation of some key genes, such as progesterone receptor and aromatase, has been associated with the silencing of these genes and might contribute to the disease. However, it is unknown whether global alterations in DNA methylation patterns occur in endometriosis and to what extent they are involved in its pathogenesis. We conducted a whole-genome scanning of methylation status in more than 25,000 promoters, using methylated DNA immunoprecipitation with hybridization to promoter microarrays. We detailed the methylation profiles for each subtype of the disease (superficial endometriosis, endometriomas, and deep infiltrating endometriosis) and compared them with the profile obtained for the eutopic endometrium. In line with the current theory of the endometrial origin of endometriosis, the overall methylation profile was highly similar between the endometrium and the lesions. It showed promoter regions consistently hypomethylated or hypermethylated (more than 1.5-times, as compared with endometrium) and others specific to one given subtype. Albeit there was no systematic correlation between promoter methylation and expression of nearby genes, 35 genes had both methylation and expressional alterations in the lesions. These genes, reported here for the first time, might be of interest in the development of endometriosis. In addition, hypermethylated regions were located at the ends of the chromosomes, whereas hypomethylated regions were randomly distributed all along the chromosomes. We postulated that this original observation might participate to the chromosomal stability and protect the endometriotic lesion against malignancy.
authors.affiliation: Département Génétique et Développement, Institut Cochin, 24 rue du Faubourg Saint-Jacques, 75014 Paris, France. bruno.borghese@inserm.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Borghese
authors.forename: Sandrine
authors.initials: S
authors.lastname: Barbaux
authors.forename: Françoise
authors.initials: F
authors.lastname: Mondon
authors.forename: Pietro
authors.initials: P
authors.lastname: Santulli
authors.forename: Guillaume
authors.initials: G
authors.lastname: Pierre
authors.forename: Giovanna
authors.initials: G
authors.lastname: Vinci
authors.forename: Charles
authors.initials: C
authors.lastname: Chapron
authors.forename: Daniel
authors.initials: D
authors.lastname: Vaiman
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004262:DNA Restriction Enzymes / Q000378:metabolism; D004715:Endometriosis / Q000145:classification / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016615:Telomere / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D007797:Laminin; D014157:Transcription Factors; C097043:laminin alpha5; D004262:DNA Restriction Enzymes; C120301:McrBC endonuclease