Global regulation of alternative splicing during myogenic differentiation
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,...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Oxford University Press
2011
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| Online Access: | http://hdl.handle.net/1721.1/66688 |
| _version_ | 1826199680527106048 |
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| author | Bland, Christopher S. Vu, Anthony David, Marjorie P. Castle, John C. Johnson, Jason M. Cooper, Thomas A. Wang, Eric T Burge, Christopher B |
| author2 | Whitaker College of Health Sciences and Technology |
| author_facet | Whitaker College of Health Sciences and Technology Bland, Christopher S. Vu, Anthony David, Marjorie P. Castle, John C. Johnson, Jason M. Cooper, Thomas A. Wang, Eric T Burge, Christopher B |
| author_sort | Bland, Christopher S. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:24:15Z |
| format | Article |
| id | mit-1721.1/66688 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:24:15Z |
| publishDate | 2011 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | mit-1721.1/666882022-09-27T19:16:32Z Global regulation of alternative splicing during myogenic differentiation Bland, Christopher S. Vu, Anthony David, Marjorie P. Castle, John C. Johnson, Jason M. Cooper, Thomas A. Wang, Eric T Burge, Christopher B Whitaker College of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Burge, Christopher B. Burge, Christopher B. Wang, Eric T. 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. National Institutes of Health (U.S.) (grant number R01GM076493) Ford Foundation (Predoctoral Diversity Fellowship) Baylor College of Medicine. Graduate School of Biomedical Sciences (Baylor Research Advocates for Student Scientists) 2011-10-31T14:58:19Z 2011-10-31T14:58:19Z 2010-07 2010-06 Article http://purl.org/eprint/type/JournalArticle 0305-1048 1362-4962 http://hdl.handle.net/1721.1/66688 Bland, C. S. et al. “Global regulation of alternative splicing during myogenic differentiation.” Nucleic Acids Research 38 (2010): 7651-7664. en_US http://dx.doi.org/10.1093/nar/gkq614 Nucleic Acids Research Creative Commons Attribution http://creativecommons.org/licenses/ by-nc/2.5 application/pdf Oxford University Press Burge |
| spellingShingle | Bland, Christopher S. Vu, Anthony David, Marjorie P. Castle, John C. Johnson, Jason M. Cooper, Thomas A. Wang, Eric T Burge, Christopher B Global regulation of alternative splicing during myogenic differentiation |
| title | Global regulation of alternative splicing during myogenic differentiation |
| title_full | Global regulation of alternative splicing during myogenic differentiation |
| title_fullStr | Global regulation of alternative splicing during myogenic differentiation |
| title_full_unstemmed | Global regulation of alternative splicing during myogenic differentiation |
| title_short | Global regulation of alternative splicing during myogenic differentiation |
| title_sort | global regulation of alternative splicing during myogenic differentiation |
| url | http://hdl.handle.net/1721.1/66688 |
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