Differential regulation of gene expression in D. melanogaster is mediated by context-specific functions of the essential CLAMP transcription factor

Urban, Jennifer Anne

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Year:: 2017
Contributor:: Urban, Jennifer Anne (creator); Larschan, Erica (Advisor); Wharton, Kristi (Reader); Kaun, Karla (Reader); Neretti, Nicola (Reader); Brown University. Department of Molecular Biology, Cell Biology and Biochemistry (sponsor)
Genre:: theses
Subject:: Drosophila melanogaster--Genetics; Genomics; Transcription factors; Chromatin; Sex determination, Genetic; dosage compensation
Extent:: 19, 146 p.
DOI: https://doi.org/10.7301/Z0B856KX

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Abstract:: Defining diverse roles of a single transcription factor on the cellular level is key to understanding its role in the context of an organism. However, for many transcription factors it is challenging to define the mechanisms that distinguish between diverse roles. The Drosophila melanogaster transcription factor Chromatin-Linked Adapter for MSL Proteins (CLAMP) provides a new model for studying context-specific functions because it has at least two spatially distinct roles. First, CLAMP mediates recruitment of the dosage compensation complex Male Specic Lethal (MSL) to the male X-chromosome. Expression of MSL complex is necessary in males, where CLAMP-mediated localization to the single male X-chromosome promotes two-fold transcriptional upregulation of most X-linked genes to equalize expression with XX females. In addition to this role, CLAMP is an essential protein that localizes to the promoters of genes throughout the genome of both males and females. To gain insight into context-specific roles for CLAMP, I have performed a comprehensive study using approaches that encompass the fields of genetics, genomics, and biochemistry. Using cell culture, I defined a role for CLAMP in regulating chromatin accessibility throughout the Drosophila genome. I further profiled nascent transcription to understand how CLAMP-mediated regulation of chromatin influences transcription. To identify the mechanisms by which CLAMP promotes differential chromatin regulation, I performed proteomics and identified many new interactions that highlight novel context-specific roles for CLAMP. Lastly, I generated the first in vivo clamp null mutant, providing the opportunity to apply the findings obtained from cell culture studies to the organism. In doing so, I revealed the importance of chromatin regulation in the context of the major developmental pathway of sex determination. In sum, I provide a comprehensive view on how a single transcription factor regulates multiple biological processes through context-specific interactions within distinct genomic locations.
Notes:: Thesis (Ph. D.)--Brown University, 2017

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Urban, Jennifer Anne, "Differential regulation of gene expression in D. melanogaster is mediated by context-specific functions of the essential CLAMP transcription factor" (2017). Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations. Brown Digital Repository. Brown University Library. https://doi.org/10.7301/Z0B856KX

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Molecular Biology, Cell Biology, and Biochemistry Theses and Dissertations

Theses and Dissertations for the Molecular Biology, Cell Biology, and Biochemistry department.
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