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Am J Hum Genet. 2016 Nov 3;99(5):1045-1058. doi: 10.1016/j.ajhg.2016.08.021. Epub 2016 Oct 27.

Allele-Specific Methylome and Transcriptome Analysis Reveals Widespread Imprinting in the Human Placenta.

Author information

1
Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
2
Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: okaehiro@m.tohoku.ac.jp.
3
Division of Epigenomics and Development, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
4
Division of Bioinformatics, Medical Institute of Bioregulation, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.
5
Department of Obstetrics, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan; Department of Gynecology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
6
Department of Informative Genetics, Environment and Genome Research Center, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan. Electronic address: tarima@med.tohoku.ac.jp.

Abstract

DNA methylation is globally reprogrammed after fertilization, and as a result, the parental genomes have similar DNA-methylation profiles after implantation except at the germline differentially methylated regions (gDMRs). We and others have previously shown that human blastocysts might contain thousands of transient maternally methylated gDMRs (transient mDMRs), whose maternal methylation is lost in embryonic tissues after implantation. In this study, we performed genome-wide allelic DNA methylation analyses of purified trophoblast cells from human placentas and, surprisingly, found that more than one-quarter of the transient-in-embryo mDMRs maintained their maternally biased DNA methylation. RNA-sequencing-based allelic expression analyses revealed that some of the placenta-specific mDMRs were associated with expression of imprinted genes (e.g., TIGAR, SLC4A7, PROSER2-AS1, and KLHDC10), and three imprinted gene clusters were identified. This approach also identified some X-linked gDMRs. Comparisons of the data with those from other mammals revealed that genomic imprinting in the placenta is highly variable. These findings highlight the incomplete erasure of germline DNA methylation in the human placenta; understanding this erasure is important for understanding normal placental development and the pathogenesis of developmental disorders with imprinting effects.

KEYWORDS:

DNA methylation; RNA sequencing; X-chromosome inactivation; genomic imprinting; germline differentially methylated region; human placenta; whole-genome bisulfite sequencing

PMID:
27843122
PMCID:
PMC5097938
DOI:
10.1016/j.ajhg.2016.08.021
[Indexed for MEDLINE]
Free PMC Article

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