DNA METHYLATION PATTERNS IN HUMAN TISSUES OF UNIPARENTAL ORIGIN USINGA ZINC-FINGER GENE (ZNF127) FROM THE ANGELMAN PRADER-WILLI REGION/

In order to further our understanding of the epigenetic modifications of DNA and its role in imprinting, we examined DNA methylation pattern s of human tissues of uniparental origin. We used complete hydatidifor m moles (CHM), which are totally androgenetic conceptions, to examine the paternal methylation pattern in the absence of a maternal contribu tion and we used ovarian teratomas to represent the maternal counterpa rt. We carried out an analysis of DNA methylation of a gene which has been shown to contain sites which are differentially methylated in a p arent-specific fashion. The gene, ZNF127, is located on chromosome 15q 11-q13 in the region associated with Prader-Willi and Angelman syndrom es. The parent-of-origin DNA methylation has been postulated to reflec t the presence of an imprint and recent studies have confirmed that ZN F127 is differentially expressed only from the paternal chromosome, We identified a unique pattern of hyper- and hypomethylated sites in and rogenetic conceptions which was nearly identical to the paternal patte rn found in sperm, This may represent the paternal germ-line methylati on imprint. We also studied partial hydatidiform moles, non-molar trip loid conceptions, normal chorionic villi, and somatic tissue, These al l demonstrated a modified DNA methylation pattern characteristic of no rmal chorionic villi with only limited findings of the imprint. Our re sults suggest that human androgenetic conceptions may provide an excel lent model to analyze epigenetic DNA modifications, such as methylatio n, in imprinted genes, The paternal allele-specific methylation imprin t will also be useful clinically to confirm the androgenetic nature of suspected molar conceptions in which parental blood samples may not b e available. (C) 1996 Wiley-Liss, Inc.