UMD Theses and Dissertations

Permanent URI for this collectionhttp://hdl.handle.net/1903/3

New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a given thesis/dissertation in DRUM.

More information is available at Theses and Dissertations at University of Maryland Libraries.

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2007 - 200912010 - 20111

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    Role of Epigenetic Modifications and Dexras1 in glucocorticoid regulation of growth hormone expression
    (2011) Narayana, Jyoti; Porter, Tom E; Molecular and Cell Biology; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Glucocorticoid induction of growth hormone in anterior pituitary cells of embryonic chickens is an indirect effect. A genome-wide microarray screen conducted on embryonic day 11 chickens identified Dexras1 as a novel candidate gene involved in mediating the glucocorticoid effects on GH mRNA expression. The following studies were aimed at characterizing glucocorticoid regulation of chicken Dexras1 and identifying potential involvement of Dexras1 in mediating glucocorticoid effects on GH expression. We determined that glucocorticoid induction of Dexras1 requires glucocorticoid receptor and both MEK1/2 and Ras cell signalling pathways. Overexpression of Dexras1 vector had no effect on GH reporter activity. Transfection of 1ng or 10ng of Dexras1 expression plasmid stimulated basal GH mRNA levels, whereas transfection of 1000ng of Dexras1 expression plasmid significantly inhibited levels of glucocorticoid-induced GH mRNA. YFP-tagged Dexras1 protein was predominantly found in the cytoplasm and glucocorticoid treatment did not cause Dexras1 to translocate to the plasma membrane. Downstream targets of Dexras1 are not known. Additionally, glucocorticoid-regulated histone modifications within 2kb of the GH gene were investigated using chromatin immunoprecipitation assays. The effects of glucocorticoid (1.5 h or 6 h) on histone H3 modifications, RNA Polymerase II (Pol II) recruitment, and association of GR, Pit-1, and Ets1 with the chicken GH gene were examined. We found increased H3 acetylation and tri-methylation of lysine 4 at both Pit-1 sites and the transcription start site (TSS) in response to 1.5 h glucocorticoid treatment. Furthermore, 1.5 h glucocorticoid treatment significantly increased recruitment of Pit-1 and Pol II to the proximal Pit-1 site and the TSS, respectively. GR was recruited to the glucocorticoid-responsive region (GCRR) and the distal Pit-1 site in response to 1.5 h glucocorticoid treatment, while 6 h glucocorticoid treatment resulted in Ets1 dissociation from the GCRR. Collectively, these results indicate that glucocorticoid induces dynamic changes in histone modifications and transcription factor recruitment within the 5'-flanking region of the chicken GH gene. We conclude that glucocorticoid induction of GH gene expression in chickens is achieved by a combination of genomic and nongenomic pathways. Our studies provide novel mechanisms of GH regulation in chickens, some of which may be found in other vertebrate species as well.
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    Identification of Novel Mechanisms in the Hypothalamus Linked to Adiposity.
    (2007-12-05) Byerly, Mardi Susanna; Porter, Tom E; Neuroscience and Cognitive Science; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Body composition is a trait regulated by many different genes, giving rise to the severity of the phenotype in a continuous manner. We propose to investigate genetic interactions regulating obesity by focusing on genetic heretibility and genes that interact with Brain-Derived Neurotrophic Factor (BDNF) or thyroid hormone. We have utilized a novel model of obesity, genetically selected chicken lines, because differences in abdominal fat between the lines are based on genotype alone, independent of environmental influences. In order to identify novel gene networks that might give rise to the obese phenotype, hypothalamic gene expression was characterized using microarray technology. Hypothalamic neuronal cell cultures and in vivo manipulations were performed to verify that BDNF interacts with the hypothalamic-pituitary-thyroid axis, while simultaneously identifying novel genes that may interact together or independently of BDNF. A hypothetical model suggesting how BDNF and thyroid hormone reciprocally modulate genes in the hypothalamus already known to contribute to energy regulation was developed.