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Computational Analysis Of Non-Cpg Dna Methylation In The Mammalian Nervous System, Dennis Yawen Wu
Computational Analysis Of Non-Cpg Dna Methylation In The Mammalian Nervous System, Dennis Yawen Wu
Arts & Sciences Electronic Theses and Dissertations
Noncanonical forms of DNA methylation, especially non-CpG DNA methylation, play essential roles in the neuronal epigenome, and have only recently begun to be characterized. While most DNA methylation within mammals is found in a CG context and maintained by DNMT1, neurons contain uniquely high levels of non-CpG methylation, such that the total amounts of methylation in non-CpG contexts equals or surpasses the total amounts of methylation in CG contexts. Non-CpG methylation, unlike CpG methylation, cannot be maintained by DNMT1, and must be established by the de novo methyltransferase DNMT3A.One unique characteristic of non-CpG methylation compared to canonical CpG methylation is …
Understanding The Roles Of Dna Methylation And Mecp2 In Neuronal Enhancer Control, Adam Clemens
Understanding The Roles Of Dna Methylation And Mecp2 In Neuronal Enhancer Control, Adam Clemens
Arts & Sciences Electronic Theses and Dissertations
The development of organisms relies on complex spatial and temporal patterning of gene expression to define cell types and facilitate their functions. Cis-regulatory elements in our genome are responsible for the control of gene expression across tissues and cell types. Regulation of these elements themselves depends on a balance of activation and repression through epigenetic modifications and molecular regulatory components. Disruption of cis-regulatory element control is emerging as a cause of neurodevelopmental disease. An important contributor to gene regulation in development is methylation of cytosine in DNA, disruption of which has been associated with disease. Notably, while all cell types …
Identify Genetic And Epigenetic Abnormalities Associated With Therapeutic Vulnerability In Human Cancers, Wen-Wei Liang
Identify Genetic And Epigenetic Abnormalities Associated With Therapeutic Vulnerability In Human Cancers, Wen-Wei Liang
Arts & Sciences Electronic Theses and Dissertations
Human cancer is a complex and dynamic disease with mutational, spatial, and temporal heterogeneity. There has been a concerted effort to address the heterogeneity by profiling large-scale multiomic datasets with an emphasis on abnormalities such as DNA mutations at coding regions and structural variants. However, a systematic analysis of alterations at “dark matter” is lacking – including DNA slippage events at microsatellite sequences, gene fusions arising from genomic rearrangements, and aberrant DNA methylations at promoter regions. This dissertation focus on developing data-driven computational analysis pipelines to study the patterns of microsatellite instability, gene fusions, and aberrant DNA methylation, and their …
Developing Tools For Identifying Tissue-Specific Epigenetic Marks And Predicting Dna Hydroxy/Methylation, Yu He
Arts & Sciences Electronic Theses and Dissertations
A single genome can derive phenotypically unique cell types through various epigenetic modifications that instruct specific gene expression patterns. Histone modifications, DNA methylation, and DNA hydroxymetylation are the most common epigenetic modifications. To understand the mechanisms how these epigenetic modifications regulate gene expression, one often needs to map these marks genome-wide through profiling methods. Firstly, for histone modifications, Roadmap Epigenomics Consortium generated The Human Reference Epigenome Map, containing thousands of genome-wide histone modification datasets that describe epigenomes of a variety of different human tissue and cell types. This map has allowed investigators to obtain a much deeper and more comprehensive …
Designing Epigenome Editing Tools To Understand The Functional Role Of Dna Methylation Changes In Cancer, James Mcdonald
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 …
Epigenomics Of Cell Fate In Development And Disease, Rebecca Faith Lowdon
Epigenomics Of Cell Fate In Development And Disease, Rebecca Faith Lowdon
Arts & Sciences Electronic Theses and Dissertations
Epigenetic features at regulatory elements provide instructive cues for transcriptional regulation during development. However, the particular epigenetic alterations necessary for proper cell fate acquisition and differentiation are not well understood. This dissertation explores the epigenetic dynamics of regulatory elements during development and uses epigenome annotations to document inappropriate transcriptional regulation in disease. First, I summarize my contributions to developing a new algorithm for detecting differential DNA methylation, M&M. I report the application of the M&M algorithm to identify distinct classes of DNA methylation dynamics in surface ectoderm (SE) progenitor cells and SE-derived lineages: epigenome alterations, and differential DNA methylation in …
On The Origin Of Phenotypic Variation: Novel Technologies To Dissect Molecular Determinants Of Phenotype, Francesco Vallania
On The Origin Of Phenotypic Variation: Novel Technologies To Dissect Molecular Determinants Of Phenotype, Francesco Vallania
All Theses and Dissertations (ETDs)
This thesis describes the conception, design, and development of novel computational tools, theoretical models, and experimental techniques applied to the dissection of molecular factors underlying phenotypic variation. The first part of my work is focused on finding rare genetic variants in pooled DNA samples, leading to the development of a novel set of algorithms, SNPseeker and SPLINTER, applied to next-generation sequencing data. The second part of my work describes the creation of a reporter system for DNA methylation for the purpose of dissecting the genetic contribution of tissue-specific patterns of DNA methylation across the genome. Finally the last part of …