Re-investigation and RNA sequencing-based identification of genes with placenta-specific imprinted expression.
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.
Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Hiroaki
H
Okae
Hitoshi
H
Hiura
Yuichiro
Y
Nishida
Ryo
R
Funayama
Satoshi
S
Tanaka
Hatsune
H
Chiba
Nobuo
N
Yaegashi
Keiko
K
Nakayama
Hiroyuki
H
Sasaki
Takahiro
T
Arima
D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D000818:Animals; D000075369:Anoctamin-1; D018118:Chloride Channels / Q000235:genetics* / Q000378:metabolism; D003656:Decidua / Q000378:metabolism; D004624:Embryo Transfer; D005260:Female; D020869:Gene Expression Profiling; D018392:Genomic Imprinting; D006801:Humans; D051379:Mice; D010750:Phosphoproteins / Q000235:genetics; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D012097:Repressor Proteins; D017423:Sequence Analysis, RNA; D013234:Stem Cells / Q000166:cytology; D014157:Transcription Factors / Q000235:genetics; D014327:Trophoblasts / Q000166:cytology
C531181:ANO1 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D000075369:Anoctamin-1; D018118:Chloride Channels; C490897:Gab1 protein, mouse; D010750:Phosphoproteins; D012097:Repressor Proteins; C527638:Sfmbt2 protein, mouse; D014157:Transcription Factors