The role of non-coding mutations in the genomic architecture of ER-positive breast cancer
File(s)
Author(s)
Al-Shehri, Seham
Type
Thesis
Abstract
In cancer, different epigenetic changes occur in genomic regions, especially in the promoters and enhancers of genes and the regulatory regions that govern transcriptional patterns. ZNF143 transcription factor binding protein is conserved in all animal species, and research has shown that ZNF143 binds to over 2000 promoters of small nuclear RNA and messenger RNA genes in metazoans. ZNF143 has been identified as a transcriptional activator, and more recently it has also been found to collaborate with the CCCTC-binding factor (CTCF) protein in topologically associated chromatin domains. However, genetic variations in the non-coding sequences that encode ZNF143 binding sites and the roles they play have not yet been investigated in great detail in breast cancer (BC). The main objectives of this study were therefore to identify potential ZNF143 binding sites and their sequence variants and to determine what effect ZNF143 binding has on changes induced in BC cells because of this binding process. Based on our analysis, we conclude that there are 90 commonly shared binding sites between the three cell lines. LTED and MCF7-FULVR share 54 binding sites while MCF7 shares only 7 binding sites with MCF7-FULVR and 2 binding sites with LTED. However, based on annotating ZNF143 peak based on the distance to the nearest Transcription Start Site (TSS), we identified 2394 genes between all the three cell lines, 1330 between LTED and MCF7-FULVR, while in MCF7 there is 87 genes shared with LTED and 213 with MCF7-FULVR. ChIP-Seq prediction and comparative analysis show that Long Term Oestrogen Depleted (LTED) cell lines contain a significant number of non-coding variants that are associated with cancer genes, and that the LTED cell line is more closely associated with transcription factors that overlap with ZNF143 than it is with MCF7-FULVR cell lines.
Version
Open Access
Date Issued
2022-06
Date Awarded
2024-12
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Magnani, Luca
Brown, Robert
Sponsor
Jāmiʻat al-Malik Saʻūd
Grant Number
136030
Publisher Department
Medicine - Surgery and Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)