Eukaryotic genomes are highly complex entities, including both classical protein-coding genes, non-coding RNA species, and a vast array of transposable elements and their remnants. One of the key challenges in the modern, genomic era is to understand how all of these elements are inter-regulated and thereby orchestrate embryonic development and maintain organismal homeostasis. The insight gained from these processes will be crucial for identifying how these systems dysfunction in the setting of disease. This dissertation describes a series of inter- related studies. The first aims to elucidate the gene regulatory function of the histone lysine-specific demethylase 1a, Kdm1a, during mouse development at the genomic level (Chapter 2). Embryonic stem (ES) cells are used as a model system for these studies due to the early lethality of Kdm1a mutant embryos. While many genes are de -repressed in Kdm1a mutant ES cells, the most robust expression changes are found in a type of endogenous retrovirus, named MuERV-L, and a group of genes that have co-opted long terminal repeats (LTRs) derived from closely related viruses. The second study (Chapter 3) builds upon the first as ES cells were found to transiently activate MuERV-L and related LTR-linked genes. During this MuERV-L+ state, the cells do not express the classic pluripotency markers. Expression analysis in oocytes and 2-cell stage embryos demonstrates that MuERV-L and related LTR-linked genes are silent in oocytes but are then highly activated following fertilization, suggesting that the MuERV-L+ cells in ES cell cultures may take on properties of early blastomeres. Chimeric mouse assays, indeed, demonstrate that MuERV-L+ cells robustly generate all embryonic and extraembryonic tissues; they are deemed totipotent. The MuERV-L+ state is found to be regulated by both cell intrinsic and extrinsic factors. The final study (Chapter 4) includes a preliminary bioinformatics analysis of MuERV -L and related endogenous retroviruses in the mouse genome. This will serve as a starting point for understanding the evolution of the LTR-driven gene network in 2-cell stage embryos and MuERV-L+ ES cells and determining whether it is present in other organisms. The possibility of MuERV-L genetic imprinting is included as part of this study