title: Differentiation of human parthenogenetic pluripotent stem cells reveals multiple tissue- and isoform-specific imprinted transcripts.
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.
authors.affiliation: 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.
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Stelzer
authors.affiliation: 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.
authors.forename: Shiran
authors.initials: S
authors.lastname: Bar
authors.affiliation: Department of Biological Chemistry, Institute of Life Sciences, Edmond J. Safra Campus-Givat Ram, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
authors.forename: Osnat
authors.initials: O
authors.lastname: Bartok
authors.affiliation: Department of Biological Chemistry, Institute of Life Sciences, Edmond J. Safra Campus-Givat Ram, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel.
authors.forename: Shaked
authors.initials: S
authors.lastname: Afik
authors.affiliation: 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.
authors.forename: Daniel
authors.initials: D
authors.lastname: Ronen
authors.affiliation: 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.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kadener
authors.affiliation: 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.
authors.forename: Nissim
authors.initials: N
authors.lastname: Benvenisty
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D057026:Induced Pluripotent Stem Cells; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D020033:Protein Isoforms