Repository logo
 

Regulatory Divergence of Transcript Isoforms in a Mammalian Model System.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Leigh-Brown, Sarah 
Goncalves, Angela 
Thybert, David 
Stefflova, Klara 
Watt, Stephen 

Abstract

Phenotypic differences between species are driven by changes in gene expression and, by extension, by modifications in the regulation of the transcriptome. Investigation of mammalian transcriptome divergence has been restricted to analysis of bulk gene expression levels and gene-internal splicing. Using allele-specific expression analysis in inter-strain hybrids of Mus musculus, we determined the contribution of multiple cellular regulatory systems to transcriptome divergence, including: alternative promoter usage, transcription start site selection, cassette exon usage, alternative last exon usage, and alternative polyadenylation site choice. Between mouse strains, a fifth of genes have variations in isoform usage that contribute to transcriptomic changes, half of which alter encoded amino acid sequence. Virtually all divergence in isoform usage altered the post-transcriptional regulatory instructions in gene UTRs. Furthermore, most genes with isoform differences between strains contain changes originating from multiple regulatory systems. This result indicates widespread cross-talk and coordination exists among different regulatory systems. Overall, isoform usage diverges in parallel with and independently to gene expression evolution, and the cis and trans regulatory contribution to each differs significantly.

Description

Keywords

Alleles, Alternative Splicing, Animals, Chimera, Enhancer Elements, Genetic, Evolution, Molecular, Exons, Female, Male, Mice, Phenotype, Polyadenylation, Promoter Regions, Genetic, RNA, Messenger, Transcription Initiation Site, Transcriptome

Journal Title

PLoS One

Conference Name

Journal ISSN

1932-6203
1932-6203

Volume Title

10

Publisher

Public Library of Science (PLoS)
Sponsorship
Cancer Research UK (C14303/A17197)
European Research Council (615584)
Cancer Research UK (20412)
Cancer Research UK (15603)