DNA methylation patterns in human tissues of uniparental origin using a 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 patterns of human tissues of uniparental origin. We used complete hydatidiform moles (CHM), which are totally androgenetic conceptions, to examine the paternal methylation pattern in the absence of a maternal contribution and we used ovarian teratomas to represent the maternal counterpart. We carried out an analysis of DNA methylation of a gene which has been shown to contain sites which are differentially methylated in a parent-specific fashion. The gene, ZNF127, is located on chromosome 15q11-q13 in the region associated with Prader-Willi and Angelman syndromes. The parent-of-origin DNA methylation has been postulated to reflect the presence of an imprint and recent studies have confirmed that ZNF127 is differentially expressed only from the paternal chromosome. We identified a unique pattern of hyper- and hypomethylated sites in androgenetic conceptions which was nearly identical to the paternal pattern found in sperm. This may represent the paternal germ-line methylation imprint. We also studied partial hydatidiform moles, non-molar triploid conceptions, normal chorionic villi, and somatic tissue. These all demonstrated a modified DNA methylation pattern characteristic of normal chorionic villi with only limited findings of the imprint. Our results suggest that human androgenetic conceptions may provide an excellent model to analyze epigenetic DNA modifications, such as methylation, in imprinted genes. The paternal allele-specific methylation imprint will also be useful clinically to confirm the androgenetic nature of suspected molar conceptions in which parental blood samples may not be available.
Mowery-Rushton
P A
PA
Department of Genetics, Magee Womens Hospital, Pittsburgh, Pennsylvania, 1521 USA.
Driscoll
D J
DJ
Nicholls
R D
RD
Locker
J
J
Surti
U
U
D017204:Angelman Syndrome / Q000235:genetics*; D004247:DNA / Q000737:chemistry*; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics; D051741:Kruppel-Like Transcription Factors; D008745:Methylation; D010051:Ovarian Neoplasms / Q000235:genetics; D011218:Prader-Willi Syndrome / Q000235:genetics*; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics*; D015183:Restriction Mapping; D013724:Teratoma / Q000235:genetics; D019076:Transgenes; D016335:Zinc Fingers
D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; C095634:ZNF174 protein, human; D004247:DNA