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

被引：95

作者：

Hamada, Hirotaka ^{[1
]}

Okae, Hiroaki ^{[1
]}

Toh, Hidehiro ^{[2
]}

Chiba, Hatsune ^{[1
]}

Hiura, Hitoshi ^{[1
]}

Shirane, Kenjiro ^{[2
]}

Sato, Tetsuya ^{[3
]}

Suyama, Mikita ^{[3
]}

Yaegashi, Nobuo ^{[4
,5
]}

Sasaki, Hiroyuki ^{[2
]}

Arima, Takahiro ^{[1
]}

机构：

[1] Tohoku Univ, Environm & Genome Res Ctr, Dept Informat Genet, Grad Sch Med, Sendai, Miyagi 9808575, Japan

[2] Kyushu Univ, Med Inst Bioregulat, Div Epigen & Dev, Fukuoka 8128582, Japan

[3] Kyushu Univ, Med Inst Bioregulat, Div Bioinformat, Higashi Ku, Maidashi 3-1-1, Fukuoka 8128582, Japan

[4] Tohoku Univ, Dept Obstet, Grad Sch Med, Sendai, Miyagi 9808575, Japan

[5] Tohoku Univ, Dept Gynecol, Grad Sch Med, Sendai, Miyagi 9808575, Japan

来源：

AMERICAN JOURNAL OF HUMAN GENETICS | 2016年 / 99卷 / 05期

关键词：

DNA METHYLATION DYNAMICS; GENE; EXPRESSION; INHERITANCE; GERMLINE; DISEASE; DNMT1; CELL;

D O I：

10.1016/j.ajhg.2016.08.021

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1045 / 1058

页数：14

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