The regulation of DNA methylation by a long non-coding RNA

Download Statistics

Downloads

Downloads per month over past year

Jones, Rhian Louise (2020). The regulation of DNA methylation by a long non-coding RNA. University of Birmingham. Ph.D.

Preview

Jones2020PhD.pdf
Text - Accepted Version
Available under License All rights reserved.
Download (22MB) | Preview

Abstract

Methylation of DNA is an epigenetic mechanism that is crucial in regulating gene expression. Aberrant changes in gene transcription observed in cancers and other diseases, is often attributed to changes in DNA methylation patterns. As a result, understanding the regulation of the DNA methyltransferase (DNMT) family of proteins, which catalyse addition of methyl groups to cytosine residues (5mC), is necessary. Recently, a number of long non-coding RNAs (lncRNAs) have been shown to play a role in regulating activity of DNA methyltransferase-1 or DNMT1. We show that our lncRNA of interest, which is frequently mutated in myeloid leukaemia, also interacts with DNMT1. In an exciting discovery, we have found that a knockout (KO) of this RNA results in DNMT1 re-localising to the cytoplasm of the cell. As a consequence, in KO cells, DNA is significantly hypomethylated and many genes show changes in expression. We also observe that KO cells grow significantly slower and are apoptotic. We have additionally seen changes in 3D nuclear architecture, although it is currently unclear how this occurs. These observations not only suggest a new role for our lncRNA in DNA methylation by regulating subcellular localisation of DNMT1, but also its potential in down- regulating cancer cell growth.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):