Re-investigation and RNA sequencing-based identification of genes with placenta-specific imprinted expression

• Published in: Human molecular genetics Vol. 21; no. 3; pp. 548 - 558
• Main Authors: Okae, Hiroaki, Hiura, Hitoshi, Nishida, Yuichiro, Funayama, Ryo, Tanaka, Satoshi, Chiba, Hatsune, Yaegashi, Nobuo, Nakayama, Keiko, Sasaki, Hiroyuki, Arima, Takahiro
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.02.2012
• Subjects: Alleles; Animals; Anoctamin-1; Biological and medical sciences; Chloride Channels - genetics; Chloride Channels - metabolism; Decidua - metabolism; DNA methylation; Embryo Transfer; epigenetics; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Genetics of eukaryotes. Biological and molecular evolution; Genomic Imprinting; Humans; Imprinting; Mice; Molecular and cellular biology; Phosphoproteins - genetics; Placenta; Placenta - metabolism; Pregnancy; RNA; Sequence Analysis, RNA; Stem cells; Stem Cells - cytology; Transcription Factors - genetics; Trophoblasts; Trophoblasts - cytology; Pregnancy; Placenta; Gene; RNA; Fetal membrane; Genetics; Identification; Sequencing; Genomic imprinting
• ISSN: 0964-6906; 1460-2083; 1460-2083
• DOI: 10.1093/hmg/ddr488

Within the vertebrate groups, only mammals are subject to a specialized epigenetic process termed genomic imprinting in which genes are preferentially expressed from one parental allele. Imprinted expression has been reported for >100 mouse genes and, for approximately one-quarter of these genes, the imprinted expression is specific to the placenta (or extraembryonic tissues). This seemingly placenta-specific imprinted expression has garnered much attention, as has the apparent lack of conserved imprinting between the human and mouse placenta. In this study, we used a novel approach to re-investigate the placenta-specific expression using embryo transfer and trophoblast stem cells. We analyzed 20 genes previously reported to show maternal allele-specific expression in the placenta, and only 8 genes were confirmed to be imprinted. Other genes were likely to be falsely identified as imprinted due to their relatively high expression in contaminating maternal cells. Next, we performed a genome-wide transcriptome assay and identified 133 and 955 candidate imprinted genes with paternal allele- and maternal allele-specific expression. Of those we analyzed in detail, 1/6 (Gab1) of the candidates for paternal allele-specific expression and only 1/269 (Ano1) candidates for maternal allele-specific expression were authentically imprinted genes. Imprinting of Ano1 and Gab1 was specific to the placenta and neither gene displayed allele-specific promoter DNA methylation. Imprinting of ANO1, but not GAB1, was conserved in the human placenta. Our findings impose a considerable revision of the current views of placental imprinting.