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Nucleosomes provides an additional layer of gene regulation by regulating chromatin accessibility. We have found that factors involved in regulating nucleosome positioning, such as SMARCA4, are recurrently mutated in lung adenocarcinoma and can be correlated with changes in alternative splicing. As a result, it is important to understand nucleosome positioning across an entire gene-body to understand how they interact to cause changes in splicing. The key in being able to understand this is using long-read sequencing methods to understand the positioning of nucleosomes at once. In my thesis, I focus on developing methods and computational tools to understand nucleosome positioning with long-reads. I developed a method called Add-seq, that uses a small molecule called angelicin to label accessible regions and determine those positions using nanopore sequencing. Based on the analyses for Add-seq, I also developed a toolkit called cawlr, a computational pipeline that can automate calling nucleosomes on single-molecules from any long-read sequencing technology. This work provides new ways of looking at nucleosomes and understanding their positioning in the context of other biological processes.

Event Host: Brandon Saint-John, Ph.D. Candidate, Biomolecular Engineering & Bioinformatics

Advisor: Angela Brooks

Join us in person or on Zoom: https://ucsc.zoom.us/j/94159043853?pwd=VW1hRitrTEt4aTJhTmFEQy8zRE1KZz09

Passcode: 819770

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