Epigenetics in mouse placental development
Abstract/Contents
- Abstract
- Epigenetic pathways are differentially regulated in embryo versus placenta. This differential regulation allows co-option of genes and gene pathways, facilitating both the evolution and function of the placenta. Alterations in these pathways have severe impacts on placental growth and health. Hence, understanding epigenetics in the placenta is of great interest. In chapter 2, I describe a genome-wide screen for placental imprinting. While mammals generally express both alleles of each gene, a small number of loci show parent-of-origin bias. This bias is called "imprinting"; it is particularly common in the placenta. I used a new methodology with improved reproducibility to identify candidate imprinted genes. I discovered bias at 78 novel genes, and a preference for the maternal allele. I found a handful of genes that escape X-inactivation. Finally, I observed striking litter-specific variation. These results underline several themes of placental imprinting: it is widespread, variable, and with a likely maternal bias. In chapter 3, I used a tissue-specific mutant mouse to determine the function of DNA methyltransferases in the placenta. These proteins are responsible for adding a methyl group to cytosines, creating a repressive mark associated with the silencing of repetitive regions as well as inactive alleles of imprinted genes. Mutants lacking DNA methyltransferase function show placental phenotypes, although the placenta is in general hypomethylated. While mutant males were viable, females died early in development. This suggests two conclusions: that DNA methylation in the placenta is not required on autosomes, and that DNA methylation plays an essential role in continued silencing of the X chromosome. Thus, in the absence of this silencing female placentas are nonfunctional and female embryos die. In chapter 4 I describe general conclusions of my work: the extraordinary epigenetic flexibility of the placenta, the importance of silencing the X chromosome, and a subtle preference for the maternal allele. I also suggest several promising avenues for future study, including examining placental histone modifications and studying cell- or cell-type-specific variation.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2014 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Finn, Elizabeth | |
|---|---|---|
| Associated with | Stanford University, Department of Genetics. | |
| Primary advisor | Baker, Julie, (Professor of genetics) | |
| Thesis advisor | Baker, Julie, (Professor of genetics) | |
| Thesis advisor | Lipsick, Joseph Steven, 1955- | |
| Thesis advisor | Sherlock, Gavin | |
| Thesis advisor | Sidow, Arend | |
| Advisor | Lipsick, Joseph Steven, 1955- | |
| Advisor | Sherlock, Gavin | |
| Advisor | Sidow, Arend |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Elizabeth Finn. |
|---|---|
| Note | Submitted to the Department of Genetics. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2014. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2014 by Elizabeth Havener Finn
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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