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Series GSE43223 Query DataSets for GSE43223
Status Public on Jun 01, 2013
Title Alternate exon switching establishes a tissue-specific transcription factor to mediate temporal activation of gene expression during differentiation
Organism Mus musculus
Experiment type Genome binding/occupancy 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 ChIP-Seq profiling of Mef2Da1 and Mef2Da2 isoforms generated by alternate splicing
Contributor(s) Sebastian S, Dilworth FJ
Citation(s) 23723416
Submission date Dec 31, 2012
Last update date May 15, 2019
Contact name Stephen Tapscott
Organization name Fred Hutch Cancer Research Center
Department Human Biology
Lab Tapscott
Street address 1100 Fairview N. Ave
City Seattle
State/province WASHINGTON
ZIP/Postal code 98103
Country USA
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (4)
GSM1058955 Mef2Da1
GSM1058956 Mef2Da2
GSM1058957 Mef2Da1-BLOCK
SRA SRP017715
BioProject PRJNA185319

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE43223_RAW.tar 250.0 Kb (http)(custom) TAR (of TXT)
GSE43223_comb.peak.csv.gz 475.4 Kb (ftp)(http) CSV
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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