Investigating the complex transcriptional relationship between intragenetic CpG islands and their host genes

Abstract

Pre-mRNA processing mechanisms such as alternative splic- ing (AS) and alternative polyadenylation (APA) generate diverse transcripts in mammalian genomes during develop- ment and tissue differentiation. Epigenetic factors including DNA methylation and histone modifications such as trimethy- lation of histone H3 lysine 36 (H3K36me3) play a role in generating transcriptome diversity. Intragenic CpG islands (iCGIs) and their corresponding host genes provide a way of examining gene expression in the context of epigenetic factors and transcriptional output resulting from AS and APA glob- ally across the genome and at high resolution at the specific model locus Mcts2/H13. Over 4000 host genes have been identified genomewide harbouring an iCGI, including both previously annotated and novel iCGI/host gene pairs. The transcriptional activity of these iCGIs is tissue- and develop- mental stage-specific and, for the first time, I demonstrate that the premature termination of host gene transcripts upstream of iCGIs is closely correlated with the level of iCGI tran- scription. My work suggest that iCGI transcription, rather than H3K36me3 or DNA methylation, interferes with host gene transcription and pre-mRNA processing genomewide and contributes to the spatiotemporal diversification of both the transcriptome and proteome.

Date of Award	1 May 2020
Original language	English
Awarding Institution	King's College London
Supervisor	Rebecca Oakey (Supervisor) & Reiner Schulz (Supervisor)