2Department of Biochemistry and Molecular Biology, Institute of Basic Medicine, Hebei Medical University, No. 361, Zhongshan East Road, Shijiazhuang 050017, China; fax: 86 (0) 311-6696826; E-mail: email@example.com
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Received October 25, 2004; Revision received July 9, 2005
Proteins of the LIM family play important roles in a variety of fundamental biological processes including cell lineage specification and organ development. Here we examined the function in cardiogenesis of a new member of the LIM family, hhLIM, by molecular analysis of early stages of cardiomyocyte differentiation in hhLIM-deficient P19 cell line and P19 cells stably overexpressing hhLIM. The results indicate that hhLIM is a potent transcriptional activator of several cardiac muscle-specific genes. Inhibition of hhLIM expression by antisense transcripts can interfere with expression of cardiac muscle genes and block development of beating cardiomyocytes in P19 embryonic stem cells. Overexpression of hhLIM in P19 cells can enhance expression of cardiac marker genes Nkx2.5 and GATA-4 and potentiate development of cardiomyocyte-like morphology. These findings suggest that, in addition to its role in activation of the cardiac genetic program, hhLIM may be the nuclear target of inductive factor for precardiac cells.
KEY WORDS: hhLIM protein, heart embryonic stem cells, cardiomyocyte differentiation