Global regulation of alternative splicing during myogenic differentiation

Christopher S. Bland, Eric T. Wang, Anthony Vu, Marjorie P. David, John C. Castle, Jason M. Johnson, Christopher B. Burge, Thomas A. Cooper

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

Abstract

Recent genome-wide analyses have elucidated the extent of alternative splicing (AS) in mammals, often focusing on comparisons of splice isoforms between differentiated tissues. However, regulated splicing changes are likely to be important in biological transitions such as cellular differentiation, or response to environmental stimuli. To assess the extent and significance of AS in myogenesis, we used splicing-sensitive microarray analysis of differentiating C2C12 myoblasts. We identified 95 AS events that undergo robust splicing transitions during C2C12 differentiation. More than half of the splicing transitions are conserved during differentiation of avian myoblasts, suggesting the products and timing of transitions are functionally significant. The majority of splicing transitions during C2C12 differentiation fall into four temporal patterns and were dependent on the myogenic program, suggesting that they are integral components of myogenic differentiation. Computational analyses revealed enrichment of many sequence motifs within the upstream and downstream intronic regions near the alternatively spliced regions corresponding to binding sites of splicing regulators. Western analyses demonstrated that several splicing regulators undergo dynamic changes in nuclear abundance during differentiation. These findings show that within a developmental context, AS is a highly regulated and conserved process, suggesting a major role for AS regulation in myogenic differentiation.

Original languageEnglish (US)
Pages (from-to)7651-7664
Number of pages14
JournalNucleic acids research
Volume38
Issue number21
DOIs
StatePublished - Nov 2010

ASJC Scopus subject areas

  • Genetics

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