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Genomic Regulation of Clock Function

Vespoli, Jessica L

Abstract Details

2015, PHD, Kent State University, College of Arts and Sciences / Department of Biological Sciences.
The suprachiasmatic nucleus(SCN) of the hypothalamus acts as an endogenous circadian clock. Individual neurons of the SCN are capable of acting as independent circadian oscillators, but the SCN exhibits a specific structural organization, with subregions that can be defined by a variety of criteria, including neuropeptide expression and cellular responses to stimuli. individual subsets of cells can show different rhythms of gene expression. Individual genes have been identified that are differentially expressed in three specific SCN subregions. 1) The ventral SCN, characterized by expression of vasoactive intestinal polypeptide (VIP), 2) the central SCN, characterized by expression of gastrin-releasing peptide (GRP), and 3) the dorsomedial SCN, characterized by expression of arginine vasopressin (AVP).In this study we hypothesized that these 3 regions were not only defined by their neuropeptide expression, but other circadian and non-circadian gene expression, thus revealing previously unknown details of the organization of the neuronal components of the SCN.. We have identified several transcripts, some not previously identified in the SCN, that are circadian across all three regions. Our current data suggests that these three SCN subregions are characterized primarily by differences in neuropeptide expression and not by any other large-scale differences in gene expression. The robustness of rhythmic expression across SCN subregions may be an indicator of genes that have critical core functions in rhythmicity or rhythmic output, and may serve to identify good target genes for investigation in rhythmic control in the SCN. In addition, we examined the potential for estrogenic regulation of circadian clock function. There is strong evidence that estrogen influences circadian clock function, at both the behavioral and molecular levels. Several previous studies have shown that estrogen affects the expression of clock genes including Per1, Per2 and Cry2. However, these studies have not shown the exact interaction between estrogen and the clock genes. In this study, we used a bioinformatic approach to examine the presence of EREs in the non-coding regions of core clock genes, including upstream and downstream regions to the next neighboring gene. This study includes elements of the positive and negative loops of the circadian clock, including Clock, Bmal, Per1, Per2, Cry1, Cry2, CK1¿, CK2¿, Reverb¿ and ROR¿. These genes were examined in several species to determine the degree of sequence conservation and thus the likelihood that EREs contribute to the transcription of circadian clock genes.
Eric Mintz (Advisor)

Recommended Citations

Citations

  • Vespoli, J. L. (2015). Genomic Regulation of Clock Function [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1449500602

    APA Style (7th edition)

  • Vespoli, Jessica. Genomic Regulation of Clock Function. 2015. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1449500602.

    MLA Style (8th edition)

  • Vespoli, Jessica. "Genomic Regulation of Clock Function." Doctoral dissertation, Kent State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=kent1449500602

    Chicago Manual of Style (17th edition)