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Applications of Genome Editing Technology in The Study of MYC Regulation
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Applications of Genome Editing Technology in The Study of MYC Regulation. |
| 개인저자 | Cumbal Guerron, Nadia I. |
| 단체저자명 | Dartmouth College. Molecular and Cellular Biology. |
| 발행사항 | [S.l.]: Dartmouth College., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 134 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-03B. Dissertation Abstract International |
| ISBN | 9781088345139 |
| 학위논문주기 | Thesis (Ph.D.)--Dartmouth College, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: Cole, Michael D. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | The MYC oncogene is overexpressed in over 70% of human cancers. Since its identification, the study of MYC has led to the discovery of the various ways through which oncogenes contribute to the ability of normal cells to become malignant. However, there are many aspects of MYC biology that remain unknown or controversial in terms of its regulation, targetability and downstream control of its targets. Here, we developed two stable cell lines expressing MYC endogenously tagged with EGFP via CRISPR/Cas9-mediated genome editing. This system allows for efficient detection of transcriptional activity of MYC as well as the resulting fusion protein while maintaining the gene expression profiles, growth factor-associated MYC induction and growth kinetics of the parental cell lines. To our knowledge, this is the first report showing endogenous monitoring of MYC expression in human colorectal adenocarcinoma through an EGFP tag, thus making it an efficient tool for high-throughput approaches such as genetic and drug screens.Making use of the cell lines generated in Chapter 2, we performed a reporter-based CRISPR knock-out screen in order to identify novel putative MYC expression suppressors. By harnessing the ability to detect EGFPhi populations through fluorescence activated cell sorting, we identified those genes that, when depleted, lead to higher levels of MYC expression. We identified many genes that have not been previously associated to MYC regulation, with the exception of the NME2 gene. Here, we find that NME2 CRISPR-driven knock-out leads to 8-fold increase of MYC expression through various target validation experiments. Importantly, our findings challenge previous controversial literature suggesting that NME2 works as a MYC activating transcription factor. |
| 일반주제명 | Genetics. |
| 언어 | 영어 |
| 바로가기 | 
: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
