LIM-only protein, CRP2, switched on smooth muscle gene activity in adult cardiac myocytes.
Smooth muscle alpha-actin gene activity appears in promyocardial cells well before cardiac myocyte differentiation and is down-regulated during the onset of rhythmic contractility and cardiac morphogenesis. The levels of LIM-only CRP2 correlated well with smooth muscle gene activity. Cardiomyocyte-specific expression of CRP2 in transgenic mice showed robust expression of smooth muscle cell-specific transcripts and protein filaments in the adult heart. Protein transduction of a recombinant CRP2 protein, fused to the protein transduction domain of HIV, into neonatal heart cells induced de novo synthesis of smooth muscle cell-specific transcripts and proteins. The LIM zinc fingers in CRP2 were found to collaborate with Brg1 of the SNF/SWI complexes, recruited serum response factor, and remodeled smooth muscle target gene chromatin through histone acetylation. CRP2 may have a cytoskeletal role, but as a nuclear protein, CRP2 acted as a potent transcription coadaptor that remodeled silent cardiac myocyte chromatin and directed serum response factor-dependent smooth muscle gene activity.
Chang
David F
DF
Center for Cardiovascular Development and Departments of Medicine and Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
Belaguli
Narasimhaswamy S
NS
Chang
Jiang
J
Schwartz
Robert J
RJ
D000199:Actins / Q000378:metabolism; D021581:Active Transport, Cell Nucleus; D000818:Animals; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D005786:Gene Expression Regulation; D006321:Heart / Q000196:embryology; D060588:LIM Domain Proteins; D051379:Mice; D008822:Mice, Transgenic; D009124:Muscle Proteins / Q000502:physiology*; D009130:Muscle, Smooth / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009687:Nuclear Proteins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015533:Transcriptional Activation
D000199:Actins; C484376:Csrp2 protein, mouse; C484375:Csrp2 protein, rat; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins