|
| Status |
Public on May 04, 2017 |
| Title |
MeDIP and hMeDIP assays using human placentas of obese and lean (healthy weight) pregnancies |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by genome tiling array
|
| Summary |
Maternal obesity has both a direct effect on the outcome of pregnancy but also programs the fetus for obesity and metabolic syndrome in later life. Due to its roles at the interface between mother and fetus, the placenta transduces and mediates the effects of the obese intrauterine environment on the fetus. Here we have generated genome-scale high-resolution maps of 5mC and 5hmC in human placentas of obese and healthy weight pregnancies. Widespread alterations to the placental epigenome identified across the genome in the setting of maternal adiposity are primarily characterized by increase in 5mC and reciprocal decrease in 5hmC. This is also evident at the two pregnancy-associated gene clusters on chromosomes 17 and 19. In addition, maternal adiposity is associated with downregulation of ten-eleven translocation (TET) and isocitrate dehydrogenase (IDH) family genes and is accompanied by decreased levels of α-ketoglutarate (αKG) in the placenta. Of note, αKG levels exhibit a close positive correlation with both ascorbate and aconitate levels and less substantial but significant association with global 5hmC levels and placenta-specific gene expression. These observations suggest a mechanistic linkage between obesogenic environment and conversion efficiency of 5mC to 5hmC and highlight the idea that TET-mediated active DNA demethylation pathway can sense and respond to metabolic derangements and plays a role in subsequent cellular adaptation. Collectively, this study demonstrates that altered DNA demethylation process is likely one of the mechanisms underlying metabolic modulation of the placental epigenome with maternal adiposity.
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| |
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| Overall design |
Comparison of lean vs obese epigenomes in human pregnancies
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| |
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| Contributor(s) |
Mitsuya K, Myatt L |
| Citation(s) |
29045485 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R21 HD076266 |
Effects of a Maternal Obesogenic Environment on DNA Methylation in the Placenta |
UNIVERSITY OF TEXAS HLTH SCI CTR SAN ANTONIO |
Leslie Myatt |
|
| Submission date |
Jun 11, 2015 |
| Last update date |
Aug 01, 2019 |
| Contact name |
Kohzoh Mitsuya |
| E-mail(s) |
mitsuya@uthscsa.edu
|
| Phone |
210-567-7064
|
| Organization name |
University of Texas Health Science Center San Antonio
|
| Department |
Center for Pregnancy and Newborn Research
|
| Lab |
Leslie Myatt
|
| Street address |
7703 Floyd Curl Drive
|
| City |
San Antonio |
| State/province |
Texas |
| ZIP/Postal code |
78229-3900 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL16284 |
NimbleGen Human DNA Methylation 2.1M Deluxe Promoter Array [100929_HG19_Deluxe_Prom_Meth_HX1] |
|
| Samples (4)
|
| GSM1708580 |
lean epigenome, 5-methylcytosine (5mC) by MeDIP |
| GSM1708581 |
obese epigenome, 5-methylcytosine (5mC) by MeDIP |
| GSM1708582 |
lean epigenome, 5-hydroxymethylcytosine (5hmC) by hMeDIP |
| GSM1708583 |
obese epigenome, 5-hydroxymethylcytosine (5hmC) by hMeDIP |
|
| Relations |
| BioProject |
PRJNA286735 |
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