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

Hirotaka Hamada, Hiroaki Okae, Hidehiro Toh, Hatsune Chiba, Hitoshi Hiura, Kenjiro Shirane, Tetsuya Sato, Mikita Suyama, Nobuo Yaegashi, Hiroyuki Sasaki, Takahiro Arima

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1045-1058
Number of pages14
JournalAmerican Journal of Human Genetics
Issue number5
Publication statusPublished - 2016 Nov 3


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


Dive into the research topics of 'Allele-Specific Methylome and Transcriptome Analysis Reveals Widespread Imprinting in the Human Placenta'. Together they form a unique fingerprint.

Cite this