Differentiation of human parthenogenetic pluripotent stem cells reveals multiple tissue and isoform specific imprinted transcripts

Parental imprinting results in a monoallelic parent-of-origin dependent gene expression. However, many imprinted genes identified by differential methylation do not exhibit complete monoallelic expression. Previous studies demonstrated a complex tissue-dependent expression patterns for some imprinted genes. Still, the complete magnitude of this phenomenon remains largely unknown. Differentiating human parthenogenetic induced pluripotent stem cells into different cell types and combining DNA methylation with novel 5' RNA sequencing methodology, enabled us to identify tissue- and isoform-dependent imprinted genes in a genome wide manner. We show that nearly half of all imprinted genes expresses both biallelic and monoallelic isoforms, that are controlled by tissue specific alternative promoters. This study provides the first global analysis of tissue-specific imprinting in humans, and implies that alternative promoters are central in the regulation of imprinted genes.

6