Life Sciences Commons^™

Conservation And Variation Of Dna Methylation In Lactuca Sativa And Lactuca Serriola, Trudi A. Baker

Graduate Doctoral Dissertations

Molecular techniques for guiding plant breeding have successfully used wild progenitors of domestic crops as sources of genetic variants conveying desirable traits. However, epigenetic variation, in particular DNA methylation, is a significant source of phenotypic variation and epigenetic effects of plant domestication are poorly understood. Described herein are the first single-base pair resolution methylomes of the highly valued crop iceberg lettuce (Lactuca sativa cv. Salinas) and its close relative, and ubiquitous weed, L. serriola. This work suggests several roles for acquisition and inheritance of methylation in the evolution of Lactuca spp. in response to stress. The Lactuca spp. have conserved …

Designing Epigenome Editing Tools To Understand The Functional Role Of Dna Methylation Changes In Cancer, James Mcdonald

Arts & Sciences Electronic Theses and Dissertations

DNA methylation is known to silence gene expression in the context of imprinting, X-chromosome inactivation, and retrotransposon silencing. However, the role of DNA methylation in silencing gene expression outside of these contexts is not fully understood. This is especially true in diseases such as cancer, where normal DNA methylation patterns are significantly altered. In breast cancer as well as nearly all cancer types, most of the genome loses DNA methylation while small regions of the genome gain methylation. DNA methylation generally correlates with decreased gene expression when present at a gene promoter. Therefore, these regions of hypo- and hyper-methylation may …

Epigenetic Response To Challenging Environmental Conditions, Marta Robertson

USF Tampa Graduate Theses and Dissertations

The discovery of epigenetic mechanisms has ignited speculation into their role in ecological and evolutionary processes. In particular, the contribution of epigenetic variation to adaptation or phenotypic plasticity that is distinct from genetic variation would be an important addition to existing evolutionary mechanisms. Although the research of epigenetic mechanisms from an ecological and evolutionary (or eco-evolutionary) perspective has been growing, it is still unclear how epigenetic variation might function in natural populations and settings and to what extent it might serve to mediate population response to changing environmental conditions over time. Over the course of my dissertation, I explored the …

Hippocampal Epigenetic Changes In A Mouse Model Of Fetal Alcohol Spectrum Disorders, Eric J. Chater-Diehl

Electronic Thesis and Dissertation Repository

Fetal alcohol spectrum disorders (FASD) refers to the neurological, developmental, and behavioural abnormalities arising from in utero ethanol exposure. These abnormities included attention deficit, anxiety, and learning and memory impairment persisting into adulthood. The molecular mechanisms of such persistent behavioural changes remain unknown and are an area of intense research. In this thesis, mice were exposed to ethanol during the third trimester equivalent, the peak of synaptic development. Following this exposure, genome-wide epigenetic and gene expression and changes in the hippocampus were assessed in adult (70 day old) mice.

In the first experiment, genome-wide trimethylation of histone H3 at histone …

Epigenetic Profiling Of Mammalian Retrotransposons, Arundhati Bakshi

LSU Doctoral Dissertations

Over evolutionary time, mammalian genomes have accumulated a large number of retrotransposons, making up about half of the genome in any given species. These retrotransposons are typically repressed by epigenetic mechanisms, one of the main ones being DNA methylation. It is well known that improper DNA methylation of retrotransposons can have unwanted consequences on nearby gene expression, and hypomethylation of retrotransposons has been frequently observed in various cancers. Nevertheless, it has been notoriously difficult to study retrotransposon loci individually due to the highly repetitive nature of their sequences. To address this issue, we have developed a novel protocol termed HT-TREBS …

Epigenetic Response Of Imprinted Domains During Carcinogenesis, Corey Lane Bretz

LSU Doctoral Dissertations

The first part of this work induced T-cell lymphoma in mice by employing a breeding scheme involving mouse strains expressing the KrasG12D oncoprotein and mice expressing cyclic recombinase from the mouse mammary tumor virus promoter. Imprinted domains were then systematically surveyed for DNA methylation changes during tumor progression using combined bisulfite restriction analysis and next-generation-bisulfite-sequencing. Hyper-or hypomethylation was detected at the imprinting control regions (ICRs) of the Dlk1, Peg10, Peg3, Grb10 and Gnas domains. These DNA methylation changes at ICRs were more prevalent and consistent than those observed at the promoter regions of well-known tumor suppressors, such as Mgmt, Fhit …

Epigenetic Editing To Validate Findings From Methylome-Wide Association Studies Of Neuropsychiatric Disorders, Robin F. Chan

Theses and Dissertations

DNA methylation is necessary for learning, memory consolidation and has been implicated in a number of neuropsychiatric disorders. Obtaining high quality and comprehensive data for the three common forms of methylation in brain is challenging for methylome-wide association studies (MWAS). To address this we optimized a panel of enrichment methods for screening the brain methylome. Results show that these enrichment techniques approach the coverage and fidelity of the current gold standard bisulfite based techniques. Our MBD-based method can also be used with low amounts of genomic material from limited human biomaterials. Psychiatric disorders have high prevalence and are often chronic …