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Transcriptional And Epigenetic Regulation Of Cerebellar Development And Function, Shahriyar Majidi May 2021

Transcriptional And Epigenetic Regulation Of Cerebellar Development And Function, Shahriyar Majidi

Arts & Sciences Electronic Theses and Dissertations

Compensation among paralogous transcription factors (TFs) confers genetic robustness of cellular processes. Despite the prevalence of this phenotypic phenomenon, an in vivo genome-scale understanding of how TFs dynamically respond within the chromatin context to paralog depletion is still lacking. We explore this question in the mammalian brain by studying the highly conserved MEF2 family of TFs, which confer phenotypic robustness for neuronal processes across multiple brain regions. The paralogous TFs MEF2A and MEF2D are strongly co-expressed in granule neurons of the cerebellum, the most abundant neurons in the brain. Employing single and double conditional knockout of MEF2A and MEF2D in …


Mapping And Functional Analysis Of Cis-Regulatory Elements In Mouse Photoreceptors, Andrew Hughes May 2019

Mapping And Functional Analysis Of Cis-Regulatory Elements In Mouse Photoreceptors, Andrew Hughes

Arts & Sciences Electronic Theses and Dissertations

Photoreceptors are light-sensitive neurons that mediate vision, and they are the most commonly affected cell type in genetic forms of blindness. In mice, there are two basic types of photoreceptors, rods and cones, which mediate vision in dim and bright environments, respectively. The transcription factors (TFs) that control rod and cone development have been studied in detail, but the cis-regulatory elements (CREs) through which these TFs act are less well understood. To comprehensively identify photoreceptor CREs in mice and to understand their relationship with gene expression, we performed open chromatin (ATAC-seq) and transcriptome (RNA-seq) profiling of FACS-purified rods and cones. …


Brain Enriched Micrornas Open The Neurogenic Potential Of Adult Human Fibroblasts, Daniel Gene Abernathy Aug 2017

Brain Enriched Micrornas Open The Neurogenic Potential Of Adult Human Fibroblasts, Daniel Gene Abernathy

Arts & Sciences Electronic Theses and Dissertations

The seemingly limitless capacities of mammals to sense, respond, and manipulate their environments stems from their structurally and functionally diverse nervous systems. Establishing these complex behaviors requires the integration of many biological phenomena including, morphogenetic gradients, cell-cell signaling, transcriptional networks, cell migration and epigenetic gene regulation. As mammalian development progresses, these pathways coordinate the production of highly specialized neuronal and glial cells, that connect and communicate with another in an even more complex manner. While evolution has shaped a multitude of pathways to produce numerous favorable traits, it has also created an intricate system vulnerable to disease. The loss of …


Epigenetic Regulation Of Lymphocyte Development And Transformation, Yue Huang May 2017

Epigenetic Regulation Of Lymphocyte Development And Transformation, Yue Huang

Arts & Sciences Electronic Theses and Dissertations

Cell identity and function rely on intricately controlled programs of gene regulation, alterations of which underlie many diseases, including cancer. Epigenetic analyses of normal and diseased cells have started to elucidate different facets of epigenetic mechanisms for gene regulation. These include changes in nucleosome density, histone modifications, factor binding and chromosomal architecture. All of these aspects contribute to the activities of regulatory elements conferring promoter, enhancer and insulator functions and the cis-regulatory circuits formed by these elements. Despite this progress, an urgent need remains to profile these features and to study how they cooperatively function in normal and pathogenic settings. …