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| Status |
Public on Jan 18, 2013 |
| Title |
Cultured Cyto and Syncytio-trophoblast samples exposed to varying degrees of hypoxia (expression) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
The mechanisms by which the placenta adapts to exogenous stimuli to create a stable and healthy environment for the growing fetus are not well known. Low oxygen tension and sub-optimal vitamin D levels influence placental function and both are associated with preeclampsia, a condition associated with altered development of placental trophoblast. We hypothesized that oxygen tension, vitamin D levels, or both affect villous trophoblast by modulation of gene expression through DNA methylation. To test this we used the Illumina Infinium Human Methylation 450 BeadChip array to compare the DNA methylation profile of primary cultures of human cytotrophoblasts and syncytiotrophoblasts under three oxygen tensions and three vitamin D levels. We found no effect on global DNA methylation by either treatment, but a limited set of loci became hypermethylated in cytotrophoblasts exposed for 24 hours to 1% oxygen, as compared to the same cells exposed to 8% or 20% oxygen. Vitamin D levels had no detectable effect on methylation profiles in either trophoblast type. Hypermethylation with low oxygen tension was independently confirmed by bisulfite-pyrosequencing in a subset of functionally important genes including CP, ITGA5, SOD2, XDH and ZNF2. Intriguingly, 70 out of the 147 hypoxia-associated CpGs, overlapped with CpG sites that become hypomethylated upon differentiation of cytotrophoblasts into syncytiotrophoblasts. Furthermore, the preponderance of altered sites was located at AP-1 binding sites. We suggest that AP-1 expression is triggered by hypoxia and interacts with DNA methyltransferases (DNMTs) to target methylation at specific sites in the genome, thus causing suppression of the associated genes that are responsible for differentiation of villous cytotrophoblast to syncytiotrophoblast.
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| Overall design |
RNA from cytotrophoblast from 2 placentas exposed to 3 different conditions of hypoxia (1%,8%,20%) and treated with 3 levels of vitamin D were run on the Illumina HT-12v4 Expression Array
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| Contributor(s) |
Yuen RC, Chen B, Blair JD, Robinson WP, Nelson DM |
| Citation(s) |
23314690 |
| Submission date |
Oct 03, 2012 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Wendy Robinson |
| E-mail(s) |
wprobinsonlab@gmail.com
|
| Organization name |
University of British Columbia
|
| Department |
Medical Genetics
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| Lab |
Robinosn
|
| Street address |
950 W 28th Ave
|
| City |
Vancouver |
| State/province |
BC |
| ZIP/Postal code |
V5Z 4H4 |
| Country |
Canada |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (15)
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| This SubSeries is part of SuperSeries: |
| GSE41341 |
Cultured Cyto and Syncytio-trophoblast samples exposed to varying degrees of hypoxia |
|
| Relations |
| BioProject |
PRJNA176596 |
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