GATA-5 is involved in leukemia inhibitory factor-responsive transcription of the beta-myosin heavy chain gene in cardiac myocytes

Leukemia inhibitory factor is a member of a family of structurally related cytokines sharing the receptor component gp130, Activation of gp130 by leuk emia inhibitory factor is sufficient to induce myocardial cell hypertrophy accompanied by specific changes in the pattern of gene expression. However, the molecular mechanisms that link gp130 activation to these changes have not been clarified. The present study investigated the transcriptional path ways by which leukemia inhibitory factor activates P-myosin heavy chain exp ression during myocardial cell hypertrophy. Mutation of the GATA motif in t he P-myosin heavy chain promoter totally abolished leukemia inhibitory fact or-responsive transcription without changing basal transcriptional activity . In contrast, endothelin-l responsiveness was unaffected by the GATA mutat ion. Among members of the cardiac GATA transcription factor subfamily (GATA -4, -5, and -6), GATA-5 was the sole and potent transactivator for the beta -myosin heavy chain promoter. This transactivation was dependent on sequenc e-specific binding of GATA-5 to the beta-myosin heavy chain GATA element, C ardiac nuclear factors that bind to to the beta-myosin heavy chain GATA ele ment were induced by leukemia inhibitory factor stimulation. Last, leukemia inhibitory factor stimulation markedly increased transcripts of cardiac GA TA-5, the expression of which is normally restricted to the early embryo. T hus, GATA-5 may be involved in gp130 signaling in cardiac myocytes.