Monoallelic expression of human PEG1/MEST is paralleled by parent-specific methylation in fetuses

Genomics
A M RiesewijkV M Kalscheuer

Abstract

We have isolated the human PEG1/MEST gene 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 that PEG1/MEST is 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 of PEG1/MEST transcripts in a lymphoblastoid cell line with maternal uniparental disomy 7. The human PEG1/MEST gene spans a genomic region of approximately 13 kb. Sequence analysis of the 5' region of PEG1/MEST revealed 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. All MspI/HpaII sites were unmethylated on the active paternal allele but methylated on the inactive maternal one.

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