COMBINATORIAL REGULATION BY ENZYMES THAT MODULATE THE CHROMATIN LANDSCAPE AND GENE EXPRESSION Public Deposited
- Last Modified
- March 22, 2019
- Creator
-
Runge, John
- Affiliation: School of Medicine, Curriculum in Genetics and Molecular Biology
- Abstract
- The eukaryotic genome is stored in the nucleus as chromatin, a dynamic structure of DNA and histone proteins. Chromatin contains a vast array of features that directs how, when, and where genomic DNA is made accessible by regulatory machinery. These features facilitate homeostatic cell programs, whereas their misregulation is a hallmark of cancer where endogenous regulatory programs are co-opted to promote aberrant signaling. In Chapter 1, I introduce four classes of proteins and protein complexes, among others, that regulate chromatin. I describe seminal discoveries that indicate these classes operate within elaborate networks that direct genomic output. In Chapter 2, I outline the roles that the class of ATP-dependent chromatin remodeling enzymes, nicknamed movers, serves in chromatin regulation. Chapters 3 and 4 describe our ongoing efforts to elucidate the mechanism by which a mover, named INO80-C, targets chromatin and identifies suitable genomic loci for regulation. We leveraged genomics approaches, biochemistry, and molecular biology to characterize the genomic targeting and molecular function of INO80-C in human cells. Chapter 3 details our observation that INO80-C is not a uniform biochemical complex at all sites across the genome, in contrast to expectations based on the literature. Chapter 4 demonstrates our efforts to delineate the function of INO80-C at its genomic targets, including our exploration of an antagonistic relationship with a histone methyltransferase named Polycomb Repressive Complex 2. Collectively, these data indicate that INO80-C engages in meaningful crosstalk with other chromatin regulators and features at its genomic targets. In Chapter 5, I draw conclusions from my research and place the findings into a broader context. Additionally, I describe the implications that my work may have on translational topics, with an emphasis on cancer biology.
- Date of publication
- May 2018
- Keyword
- DOI
- Resource type
- Advisor
- Calabrese, Mauro
- Magnuson, Terry
- Kim, William
- Davis, Ian
- Crawford, Gregory
- Degree
- Doctor of Philosophy
- Degree granting institution
- University of North Carolina at Chapel Hill Graduate School
- Graduation year
- 2018
- Language
- Parents:
This work has no parents.
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Runge_unc_0153D_17528.pdf | 2019-04-10 | Public |
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PREMIS_Events_Metadata_0_83cc433d-3125-40d0-a890-3812eb056c5a.txt | 2019-04-10 | Public |
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original_metadata_file_83cc433d-3125-40d0-a890-3812eb056c5a.xml | 2019-04-10 | Public |
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