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Tissue-specific splicing of a ubiquitously expressed transcription factor is essential for muscle differentiation

Overview of attention for article published in Genes & Development, May 2013
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2 tweeters
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1 Facebook page

Citations

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69 Dimensions

Readers on

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108 Mendeley
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1 CiteULike
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Title
Tissue-specific splicing of a ubiquitously expressed transcription factor is essential for muscle differentiation
Published in
Genes & Development, May 2013
DOI 10.1101/gad.215400.113
Pubmed ID
Authors

S. Sebastian, H. Faralli, Z. Yao, P. Rakopoulos, C. Palii, Y. Cao, K. Singh, Q.-C. Liu, A. Chu, A. Aziz, M. Brand, S. J. Tapscott, F. J. Dilworth

Abstract

Alternate splicing contributes extensively to cellular complexity by generating protein isoforms with divergent functions. However, the role of alternate isoforms in development remains poorly understood. Mef2 transcription factors are essential transducers of cell signaling that modulate differentiation of many cell types. Among Mef2 family members, Mef2D is unique, as it undergoes tissue-specific splicing to generate a muscle-specific isoform. Since the ubiquitously expressed (Mef2Dα1) and muscle-specific (Mef2Dα2) isoforms of Mef2D are both expressed in muscle, we examined the relative contribution of each Mef2D isoform to differentiation. Using both in vitro and in vivo models, we demonstrate that Mef2D isoforms act antagonistically to modulate differentiation. While chromatin immunoprecipitation (ChIP) sequencing analysis shows that the Mef2D isoforms bind an overlapping set of genes, only Mef2Dα2 activates late muscle transcription. Mechanistically, the differential ability of Mef2D isoforms to activate transcription depends on their susceptibility to phosphorylation by protein kinase A (PKA). Phosphorylation of Mef2Dα1 by PKA provokes its association with corepressors. Conversely, exon switching allows Mef2Dα2 to escape this inhibitory phosphorylation, permitting recruitment of Ash2L for transactivation of muscle genes. Thus, our results reveal a novel mechanism in which a tissue-specific alternate splicing event has evolved that permits a ubiquitously expressed transcription factor to escape inhibitory signaling for temporal regulation of gene expression.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 108 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 <1%
Netherlands 1 <1%
Russia 1 <1%
China 1 <1%
Unknown 104 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 28 26%
Researcher 24 22%
Student > Master 10 9%
Student > Bachelor 9 8%
Professor 9 8%
Other 25 23%
Unknown 3 3%
Readers by discipline Count As %
Agricultural and Biological Sciences 60 56%
Biochemistry, Genetics and Molecular Biology 30 28%
Medicine and Dentistry 5 5%
Neuroscience 3 3%
Computer Science 1 <1%
Other 3 3%
Unknown 6 6%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 August 2013.
All research outputs
#7,737,186
of 12,367,469 outputs
Outputs from Genes & Development
#4,157
of 4,996 outputs
Outputs of similar age
#78,140
of 146,742 outputs
Outputs of similar age from Genes & Development
#23
of 37 outputs
Altmetric has tracked 12,367,469 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 4,996 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 4th percentile – i.e., 4% of its peers scored the same or lower than it.
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We're also able to compare this research output to 37 others from the same source and published within six weeks on either side of this one. This one is in the 18th percentile – i.e., 18% of its contemporaries scored the same or lower than it.