Regulation of J6 gene expression by transcription factor GATA-4

Retinoic acid-induced differentiation of mouse F9 embryonal carcinoma cells into primitive endoderm is accompanied by increased transcription of the gene for J6, a heat shock protein implicated in collagen biosynthesis. In this paper we present evidence that transcription factor GATA-4, a retinoic acid-inducible GATA-binding protein, is involved in the regulation of J6 gene expression in F9 cells. Northern-blot analysis indicates that transcripts encoding GATA-4 and J6 increase in parallel during retinoic acid-induced differentiation of F9 cells. Gel-shift experiments and antibody binding studies demonstrate that: (1) GATA-4 is the major GATA-binding protein activity in differentiated F9 cells, and (2) GATA-4 binds to consensus GATA motifs in the retinoic acid-responsive portion of the J6 promoter. Co-transfection studies using NIH 3T3 cells show that GATA-4 is a potent trans-activator of the J6 promoter. These lines of evidence suggest that expression of J6 in F9 cells is regulated by GATA-4. We speculate that transcription factor GATA-4 may also control other genes involved in extracellular matrix formation in the yolk sac.