Regulation of Epstein-Barr virus gene expression via CRISPR-mediated targeting of DNA methylation enzymes

Epstein-Barr virus (EBV) can establish an oncogenic presence in cells to cause transformation. Globally, EBV drives a number of human cancers, including Natural Killer/T cell Lymphoma (NKTL). NKTL is an aggressive malignancy thought to express a limited number of EBV proteins, namely EBV nuclear...

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Main Author: Auni Afiqoh Binte Roseazam
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Format: Final Year Project
Language:English
Published: Nanyang Technological University 2024
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Online Access:https://hdl.handle.net/10356/176099
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spelling sg-ntu-dr.10356-1760992024-05-20T15:33:17Z Regulation of Epstein-Barr virus gene expression via CRISPR-mediated targeting of DNA methylation enzymes Auni Afiqoh Binte Roseazam - School of Biological Sciences A*STAR Singapore Immunology Network Wang Liang Wei wang_liang_wei@immunol.astar.edu.sg Medicine, Health and Life Sciences Epstein-Barr virus (EBV) can establish an oncogenic presence in cells to cause transformation. Globally, EBV drives a number of human cancers, including Natural Killer/T cell Lymphoma (NKTL). NKTL is an aggressive malignancy thought to express a limited number of EBV proteins, namely EBV nuclear antigen 1 (EBNA1) and latent membrane proteins (LMPs) 1 and 2. However, apart from these, NKTLs also express a wide range of EBV transcripts that do not appear to be translated. LMP1 transcript levels have been positively correlated whereas late lytic gene levels are negatively correlated with patient survival. The regulation of LMP1 and lytic gene expression is not fully understood. Therefore, in this study, the role of DNA methylation enzymes, DNMT1, DNMT3A and UHRF1, in regulating LMP1, BZLF1 and BRRF2 were clarified. Additionally, LMP1 was investigated for its regulation on these genes. Through gene editing and expression analyses, DNMT1, UHRF1, DNMT3A downregulate LMP1 expression. Intriguingly, while DNMT3A downregulated lytic genes, DNMT1 and UHRF1 upregulated BZLF1 and BRRF2, contrary to current understanding. Furthermore, LMP1 influences both latency and lytic gene expression. Thus, DNMT1, DNMT3A, UHRF1 and LMP1 could be potential targets in increasing immunogenicity in NKTL in order to enhance immune clearance of tumour mass. Bachelor's degree 2024-05-14T01:05:44Z 2024-05-14T01:05:44Z 2024 Final Year Project (FYP) Auni Afiqoh Binte Roseazam (2024). Regulation of Epstein-Barr virus gene expression via CRISPR-mediated targeting of DNA methylation enzymes. Final Year Project (FYP), Nanyang Technological University, Singapore. https://hdl.handle.net/10356/176099 https://hdl.handle.net/10356/176099 en application/pdf Nanyang Technological University
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Medicine, Health and Life Sciences
spellingShingle Medicine, Health and Life Sciences
Auni Afiqoh Binte Roseazam
Regulation of Epstein-Barr virus gene expression via CRISPR-mediated targeting of DNA methylation enzymes
description Epstein-Barr virus (EBV) can establish an oncogenic presence in cells to cause transformation. Globally, EBV drives a number of human cancers, including Natural Killer/T cell Lymphoma (NKTL). NKTL is an aggressive malignancy thought to express a limited number of EBV proteins, namely EBV nuclear antigen 1 (EBNA1) and latent membrane proteins (LMPs) 1 and 2. However, apart from these, NKTLs also express a wide range of EBV transcripts that do not appear to be translated. LMP1 transcript levels have been positively correlated whereas late lytic gene levels are negatively correlated with patient survival. The regulation of LMP1 and lytic gene expression is not fully understood. Therefore, in this study, the role of DNA methylation enzymes, DNMT1, DNMT3A and UHRF1, in regulating LMP1, BZLF1 and BRRF2 were clarified. Additionally, LMP1 was investigated for its regulation on these genes. Through gene editing and expression analyses, DNMT1, UHRF1, DNMT3A downregulate LMP1 expression. Intriguingly, while DNMT3A downregulated lytic genes, DNMT1 and UHRF1 upregulated BZLF1 and BRRF2, contrary to current understanding. Furthermore, LMP1 influences both latency and lytic gene expression. Thus, DNMT1, DNMT3A, UHRF1 and LMP1 could be potential targets in increasing immunogenicity in NKTL in order to enhance immune clearance of tumour mass.
author2 -
author_facet -
Auni Afiqoh Binte Roseazam
format Final Year Project
author Auni Afiqoh Binte Roseazam
author_sort Auni Afiqoh Binte Roseazam
title Regulation of Epstein-Barr virus gene expression via CRISPR-mediated targeting of DNA methylation enzymes
title_short Regulation of Epstein-Barr virus gene expression via CRISPR-mediated targeting of DNA methylation enzymes
title_full Regulation of Epstein-Barr virus gene expression via CRISPR-mediated targeting of DNA methylation enzymes
title_fullStr Regulation of Epstein-Barr virus gene expression via CRISPR-mediated targeting of DNA methylation enzymes
title_full_unstemmed Regulation of Epstein-Barr virus gene expression via CRISPR-mediated targeting of DNA methylation enzymes
title_sort regulation of epstein-barr virus gene expression via crispr-mediated targeting of dna methylation enzymes
publisher Nanyang Technological University
publishDate 2024
url https://hdl.handle.net/10356/176099
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