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Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Am+J+Hum+Genet 2016 ; 99 (5): 1045-1058 Nephropedia Template TP
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Allele-Specific Methylome and Transcriptome Analysis Reveals Widespread Imprinting in the Human Placenta #MMPMID27843122
Hamada H; Okae H; Toh H; Chiba H; Hiura H; Shirane K; Sato T; Suyama M; Yaegashi N; Sasaki H; Arima T
Am J Hum Genet 2016[Nov]; 99 (5): 1045-1058 PMID27843122show ga
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.
|*Alleles[MESH]
|*Gene Expression Profiling[MESH]
|*Genomic Imprinting[MESH]
|Apoptosis Regulatory Proteins[MESH]
|Blastocyst/cytology/metabolism[MESH]
|DNA Methylation[MESH]
|Exome[MESH]
|Female[MESH]
|Genes, X-Linked[MESH]
|Genome, Human[MESH]
|Genome-Wide Association Study[MESH]
|Humans[MESH]
|Intracellular Signaling Peptides and Proteins/genetics/metabolism[MESH]