DNA methylation in early mammalian development
Name
858804524-MIT.pdf
Description
Full printable version
Size
11.28 MB
Format
Adobe PDF
Checksum (MD5)
b7511ab252ab1558d4b29d0548bffefb
Author(s)
Chan, Michelle M. (Michelle Mei Wah)
Advisor(s)
Aviv Regev.
Alternative Title
Deoxyribonucleic acid methylation in early mammalian development
Date Issued
2013
Publisher
Massachusetts Institute of Technology
Abstract
All the cells in the body contain the same genome yet showcase drastically different phenotypes. This is the result of different transcriptional programs, which are partly controlled by epigenetic modifications, including DNA methylation. In this thesis, I analyze genome-scale DNA methylation profiles across pre-implantation development to identify the targets and characterize the dynamics of global demethylation that lead to totipotency and the subsequent changes to embryonic specification. In Chapter 1, I validate and refine the decades old model for DNA methylation in mouse embryogenesis, identify many retrotransposons with active DNA methylation signatures at fertilization, and discover many, novel differentially methylated regions between the gametes that exist transiently during early development. Notably, the majority of epigenetic events unique to mammalian pre-implantation development are characterized in mouse. In Chapter 2, 1 describe the DNA methylation dynamics in human preimplantation development and show that the regulatory principles that operate in mouse are conserved, though some of their targets are species-specific and define regions of local divergence. Finally, in Chapter 3, I compare DNA methylation dynamics of fertilization to an artificial reprogramming process, somatic cell nuclear transfer, in mouse, and find that most dynamics are conserved but occur at a smaller magnitude after artificial reprogramming. I conclude this thesis with a summary of the chapters and a brief discussion of ongoing and future work.
Description
Thesis (Ph. D.)--Massachusetts Institute of Technology, Computational and Systems Biology Program, 2013.
Cataloged from PDF version of thesis.
Includes bibliographical references.
Subjects
Computational and Systems Biology Program.
MIT Department
Massachusetts Institute of Technology. Computational and Systems Biology Program
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