Regulatory Divergence of Transcript Isoforms in a Mammalian Model System

PloS One
Sarah Leigh-BrownDuncan T Odom

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 ...Continue Reading

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Methods Mentioned

BETA
RNAseq
RNA-Seq

Software Mentioned

RNASeq
Ensembl
Transpath
Transfac
Bowtie
Scripture
Genetrail
R scripts
MMSEQ
Ensembl Effect Predictor

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