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Global regulation of alternative splicing during myogenic differentiation.

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Bland CS,Wang ET,Vu A,David MP,Castle JC,Johnson JM,Burge CB,Cooper TA

doi

10.1093/nar/gkq614

subject

Has Abstract

pub_date

2010-11-01 00:00:00

pages

7651-64

issue

21

eissn

0305-1048

issn

1362-4962

pii

gkq614

journal_volume

38

pub_type

杂志文章

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