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Series GSE46363 Query DataSets for GSE46363
Status Public on Jun 03, 2013
Title RNA-Seq profiling of C2C12 cells with exogenous expression of Mef2Da1 and Mef2Da2
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Although splicing occurs in most multi-exon genes, the generation of distinct isoforms through the alternate use of mutually exclusive exons is less prevalent. As exon-switching events have the potential to give rise to isoforms with different cellular functions, we have explored the role of the muscle-specific (Mef2Da2) and ubiquitously expressed (Mef2Da1) isoforms of the transcription factor Mef2D in myogenesis. Here we show that both isoforms of Mef2D bind a largely overlapping subset of genomic loci, yet only the muscle-specific Mef2Da2 isoform can activate the late myogenic gene expression program. This differential ability to activate transcription is modulated by PKA signaling where Mef2Da1 is efficiently phosphorylated by the kinase to enhance its association with repressive HDAC-deacetylase complexes. In contrast, alternate exon usage in Mef2Da2 renders the protein resistant to PKA phosphorylation, allowing it to interact with transcriptionally permissive Ash2L-trithorax complex. Our findings support a model wherein alternative exon usage allows Mef2D to transition from a repressor to activator in a myogenic environment rich in PKA activity. Thus we have identified a novel paradigm in which a ubiquitously expressed transcription factor has evolved to undergo tissue-specific alternative exon usage to permit the proper temporal activation of a gene expression program during differentiation.
Overall design RNA-Seq profiling of C2C12 cells with exogenous expression of Mef2Da1 and Mef2Da2
Contributor(s) Sebastian S, Chu A, Dilworth JF
Citation(s) 23723416
Submission date Apr 24, 2013
Last update date May 15, 2019
Contact name Marjorie Brand
Organization name Ottawa Hospital Research Institute
Street address 501 Smyth Road
City Ottawa
State/province Ontario
ZIP/Postal code K1H 8L6
Country Canada
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (3)
GSM1129195 RNASeq_C2C12_Control
GSM1129196 RNASeq_C2C12_Mef2D_Alpha
GSM1129197 RNASeq_C2C12_Mef2D_Prime
BioProject PRJNA198810
SRA SRP021492

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Supplementary file Size Download File type/resource
GSE46363_RAW.tar 575.4 Mb (http)(custom) TAR (of BEDGRAPH)
GSE46363_genes.fpkm_tracking.gz 1.2 Mb (ftp)(http) FPKM_TRACKING
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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