A New Mechanism for Genomic Nucleosome Positioning by Native ISWI and Engineered CHD Chromatin Remodeling Proteins is Driven by Sequence-Specific DNA Binding.
| dc.contributor.advisor | Selker, Eric | |
| dc.contributor.author | Donovan, Drake | |
| dc.date.accessioned | 2021-09-13T18:37:29Z | |
| dc.date.available | 2021-09-13T18:37:29Z | |
| dc.date.issued | 2021-09-13 | |
| dc.description.abstract | Encoded within DNA are all the instructions that a cell needs to survive, and these instructions must be regulated such that cells take the appropriate actions in response to environmental and developmental cues. One way that the DNA is regulated is that a portion of it is wrapped around proteins to form structures known as nucleosomes, which makes the wrapped DNA inaccessible to the machinery that reads the genetic code. Thus, the location of these nucleosome structures on the DNA plays a large role in which genes are active at what times. The location of nucleosomes on the DNA is partially regulated by a family of enzymes called chromatin remodeling proteins. While the function of chromatin remodeling proteins to position nucleosomes is well understood, the mechanisms by which they do so have not been thoroughly tested and are thought to be non-specific. It is unknown, for example, how chromatin remodeling proteins know when and where to position a nucleosome on a given DNA sequence. Reconciling how these supposedly non-specific molecular machines result in highly specific chromatin structures is the focus of this dissertation. The first part of this work challenges the idea that a chromatin remodeling protein in yeast, Isw2, acts as a non-specific nucleosome spacer. Instead, the use of biochemical and genomic techniques shows us that Isw2 is directly targeted to particular nucleosomes in a sequence-specific manner through interactions with other proteins. Further, it suggests that this mechanism may potentially exist in humans. In the second part of this work, we use the idea of sequence-specific targeting seen in Isw2 to engineer another chromatin remodeling protein, Chd1. This allows us to directly target particular nucleosomes in a synthetic manner both in test tubes and in living cells. Excitingly, we show that the use of these engineered proteins allows us to control DNA access and downstream biological outputs in yeast. Overall, this dissertation contributes a completely new understanding of how chromatin remodeling proteins can be directed to act on specific target nucleosomes both natively in eukaryotes and synthetically by researchers. This dissertation includes previously published co-authored material. | en_US |
| dc.identifier.uri | https://hdl.handle.net/1794/26637 | |
| dc.language.iso | en_US | |
| dc.publisher | University of Oregon | |
| dc.rights | All Rights Reserved. | |
| dc.title | A New Mechanism for Genomic Nucleosome Positioning by Native ISWI and Engineered CHD Chromatin Remodeling Proteins is Driven by Sequence-Specific DNA Binding. | |
| dc.type | Electronic Thesis or Dissertation | |
| thesis.degree.discipline | Department of Chemistry and Biochemistry | |
| thesis.degree.grantor | University of Oregon | |
| thesis.degree.level | doctoral | |
| thesis.degree.name | Ph.D. |
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