Parental imprinting results in monoallelic parent-oforigin- dependent gene expression. However, many imprinted genes identified by differential methylation do not exhibit complete monoallelic expression. Previous studies demonstrated complex tissue-dependent expression patterns for some imprinted genes. Still, the complete magnitude of this phenomenon remains largely unknown. By differentiating human parthenogenetic induced pluripotent stem cells into different cell types and combining DNA methylation with a 50 RNA sequencing methodology, we were able to identify tissue- and isoform-dependent imprinted genes in a genome-wide manner.We demonstrate that nearly half of all imprinted genes express both biallelic and monoallelic isoforms that are controlled by tissue-specific alternative promoters. This study provides a global analysis of tissue-specific imprinting in humans and suggests that alternative promoters are central in the regulation of imprinted genes.
Bibliographical noteFunding Information:
N.B. is supported by the Israel Science Foundation-Morasha Foundation (grant number 1252/12), by the Israel Ministry of Science and Technology Infrastructure (grant number 3-9693), by the Rosetrees Trust, and by the Azrieli Foundation. Y.S. is supported by a Human Frontier Science Program postdoctoral fellowship. D.R. is supported by the Israel Cancer Research Fund. S.K. is supported by the HFSP Program Grant (grant number 31/2011) and by the Israel Science Foundation-Morasha Foundation (grant number 839/10).