Monoallelic Expression of HumanPEG1/MESTIs Paralleled by Parent-Specific Methylation in Fetuses

Abstract

We have isolated the humanPEG1/MESTgene and have investigated its imprinting status and parental-specific methylation. FISH mapping assigned the gene to chromosome 7q32, and homologous sequences were identified on the short arm of human chromosomes 3 and 5. Through the use of a newly identified intragenic polymorphism, expression analysis revealed thatPEG1/MESTis monoallelically transcribed in all fetal tissues examined. In two informative cases, expression was shown to be confined to the paternally derived allele. In contrast to the monoallelic expression observed in fetal tissues, biallelic expression was evident in adult blood lymphocytes. Biallelic expression in blood is supported by the demonstration ofPEG1/MESTtranscripts in a lymphoblastoid cell line with maternal uniparental disomy 7. The humanPEG1/MESTgene spans a genomic region of approximately 13 kb. Sequence analysis of the 5′ region ofPEG1/MESTrevealed the existence of a 620-bp-long CpG island that extends from the putative promoter region into intron 1. We demonstrate that this CpG island is methylated in a parent-of-origin-specific manner. AllMspI/HpaII sites were unmethylated on the active paternal allele but methylated on the inactive maternal one.