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Cell Rep. 2015 Apr 14;11(2):308-20. doi: 10.1016/j.celrep.2015.03.023. Epub 2015 Apr 2.

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

Author information

1
Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Institute of Life Sciences, Edmond J. Safra Campus-Givat Ram, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel; Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.
2
Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Institute of Life Sciences, Edmond J. Safra Campus-Givat Ram, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
3
Department of Biological Chemistry, Institute of Life Sciences, Edmond J. Safra Campus-Givat Ram, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
4
Department of Biological Chemistry, Institute of Life Sciences, Edmond J. Safra Campus-Givat Ram, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel. Electronic address: skadener@gmail.com.
5
Azrieli Center for Stem Cells and Genetic Research, Department of Genetics, Institute of Life Sciences, Edmond J. Safra Campus-Givat Ram, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel. Electronic address: nissimb@mail.huji.ac.il.

Abstract

Parental imprinting results in monoallelic parent-of-origin-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 5' 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.

PMID:
25843718
DOI:
10.1016/j.celrep.2015.03.023
[Indexed for MEDLINE]
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