LIM-only protein, CRP2, switched on smooth muscle gene activity in adult cardiac myocytes

doi:10.1073/pnas.0605635103

LIM-only protein, CRP2, switched on smooth muscle gene activity in adult cardiac myocytes

*Center for Cardiovascular Development and
Departments of ^†Medicine and
^§Surgery, Baylor College of Medicine, Houston, TX 77030; and
^¶Center for Molecular Development and Diseases, Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030

Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved October 25, 2006 (received for review July 5, 2006)

Abstract

Smooth muscle α-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.

Footnotes

^‖To whom correspondence should be addressed at:
Institute of Biosciences and Technology, Center for Molecular Development and Diseases, Texas A&M University, 2121 Holcombe Boulevard, Houston, Texas 77030-3303.
E-mail: rschwartz{at}ibt.tamhsc.edu
Author contributions: D.F.C. and R.J.S. designed research; D.F.C. and N.S.B. performed research; N.S.B. and J.C. contributed new reagents/analytic tools; D.F.C. and R.J.S. analyzed data; and D.F.C. and R.J.S. wrote the paper.
↵ ^‡Present address: Division of Bone Marrow Transplant, Childrens Hospital Los Angeles, 4650 Sunset Boulevard, Los Angeles, CA 90027.
The authors declare no conflict of interest.
This article is a PNAS direct submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0605635103/DC1.
Abbreviations:

α MHC,

α-myosin heavy chain;

SMA,

smooth muscle α-actin;

SMC,

smooth muscle cell.