scholarly journals microRNA-1 regulates sarcomere formation and suppresses smooth muscle gene expression in the mammalian heart

eLife ◽  
2013 ◽  
Vol 2 ◽  
Author(s):  
Amy Heidersbach ◽  
Chris Saxby ◽  
Karen Carver-Moore ◽  
Yu Huang ◽  
Yen-Sin Ang ◽  
...  

microRNA-1 (miR-1) is an evolutionarily conserved, striated muscle-enriched miRNA. Most mammalian genomes contain two copies of miR-1, and in mice, deletion of a single locus, miR-1-2, causes incompletely penetrant lethality and subtle cardiac defects. Here, we report that deletion of miR-1-1 resulted in a phenotype similar to that of the miR-1-2 mutant. Compound miR-1 knockout mice died uniformly before weaning due to severe cardiac dysfunction. miR-1-null cardiomyocytes had abnormal sarcomere organization and decreased phosphorylation of the regulatory myosin light chain-2 (MLC2), a critical cytoskeletal regulator. The smooth muscle-restricted inhibitor of MLC2 phosphorylation, Telokin, was ectopically expressed in the myocardium, along with other smooth muscle genes. miR-1 repressed Telokin expression through direct targeting and by repressing its transcriptional regulator, Myocardin. Our results reveal that miR-1 is required for postnatal cardiac function and reinforces the striated muscle phenotype by regulating both transcriptional and effector nodes of the smooth muscle gene expression network.

2005 ◽  
Vol 25 (1) ◽  
pp. 364-376 ◽  
Author(s):  
Dongsun Cao ◽  
Zhigao Wang ◽  
Chun-Li Zhang ◽  
Jiyeon Oh ◽  
Weibing Xing ◽  
...  

ABSTRACT Differentiation of smooth muscle cells is accompanied by the transcriptional activation of an array of muscle-specific genes controlled by serum response factor (SRF). Myocardin is a cardiac and smooth muscle-specific expressed transcriptional coactivator of SRF and is sufficient and necessary for smooth muscle gene expression. Here, we show that myocardin induces the acetylation of nucleosomal histones surrounding SRF-binding sites in the control regions of smooth muscle genes. The promyogenic activity of myocardin is enhanced by p300, a histone acetyltransferase that associates with the transcription activation domain of myocardin. Conversely, class II histone deacetylases interact with a domain of myocardin distinct from the p300-binding domain and suppress smooth muscle gene activation by myocardin. These findings point to myocardin as a nexus for positive and negative regulation of smooth muscle gene expression by changes in chromatin acetylation.


2005 ◽  
Vol 280 (10) ◽  
pp. 9719-9727 ◽  
Author(s):  
Yan Liu ◽  
Sanjay Sinha ◽  
Oliver G. McDonald ◽  
Yueting Shang ◽  
Mark H. Hoofnagle ◽  
...  

2011 ◽  
Vol 3 (1) ◽  
pp. 138-145 ◽  
Author(s):  
Xiaojie Zhang ◽  
He Meng ◽  
Mila Blaivas ◽  
Elisabeth J. Rushing ◽  
Brian E. Moore ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document