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Analysis of early C2C12 myogenesis identifies stably and differentially expressed transcriptional regulators whose knock-down inhibits myoblast differentiation
- Source :
- Physiological Genomics. 44:183-197
- Publication Year :
- 2012
- Publisher :
- American Physiological Society, 2012.
-
Abstract
- Myogenesis is a tightly controlled process involving the transcriptional activation and repression of thousands of genes. Although many components of the transcriptional network regulating the later phases of myogenesis have been identified, relatively few studies have described the transcriptional landscape during the first 24 h, when myoblasts commit to differentiate. Through dense temporal profiling of differentiating C2C12 myoblasts, we identify 193 transcriptional regulators (TRs) whose expression is significantly altered within the first 24 h of myogenesis. A high-content shRNA screen of 77 TRs involving 427 stable lines identified 42 genes whose knockdown significantly inhibits differentiation of C2C12 myoblasts. Of the TRs that were differentially expressed within the first 24 h, over half inhibited differentiation when knocked down, including known regulators of myogenesis ( Myod1, Myog, and Myf5), as well as 19 TRs not previously associated with this process. Surprisingly, a similar proportion (55%) of shRNAs targeting TRs whose expression did not change also inhibited C2C12 myogenesis. We further show that a subset of these TRs inhibits myogenesis by downregulating expression of known regulatory and structural proteins. Our findings clearly illustrate that several TRs critical for C2C12 myogenesis are not differentially regulated, suggesting that approaches that focus functional studies on differentially-expressed transcripts will fail to provide a comprehensive view of this complex process.
- Subjects :
- Genetics
Regulation of gene expression
animal structures
Physiology
Myogenesis
Cellular differentiation
Down-Regulation
Cell Differentiation
Biology
Muscle Development
Myoblasts
Mice
Gene Expression Regulation
Transcription (biology)
Gene Knockdown Techniques
Gene expression
Animals
RNA, Small Interfering
Muscle, Skeletal
C2C12
Gene
Psychological repression
Transcription Factors
Subjects
Details
- ISSN :
- 15312267 and 10948341
- Volume :
- 44
- Database :
- OpenAIRE
- Journal :
- Physiological Genomics
- Accession number :
- edsair.doi.dedup.....8759ec459f015be7687fdc0cf5f6c7b0