IDENTIFICATION OF A GATA MOTIF IN THE CARDIAC ALPHA-MYOSIN HEAVY-CHAIN-ENCODING GENE AND ISOLATION OF A HUMAN GATA-4 CDNA

In an attempt to identify the cardiac-specific genes regulated by the transcription factor GATA-4, we have identified a putative GATA-binding site located within the 5' flanking sequence of the human cardiac alpha-myosin heavy-chain-encoding gene. The 23-bp sequence surrounding the core GATA-binding site is conserved across species. The core motif and flanking sequences of this GATA-binding site are almost identical to that of a well-established GATA-binding site located within the 3' enhancer of the human beta-globin gene. Using electrophoretic mobility shift analysis, two distinct nuclear factors were found to bind specifically to this element, We have isolated a full-length cDNA clone for human GATA-4 (hGATA-4) by screening a human heart cDNA library, The hGATA-4 cDNA sequence shows 85% identity with murine GATA-4 in the protein coding region, The deduced amino-acid sequence within the two zinc-finger DNA-binding domains of human GATA-4 is 100% identical with murine GATA-4, Northern blot analysis reveals that this 4.4-kb transcript has higher expression in adult heart than in fetal heart, Our results suggest that GATA-4 may regulate a set of cardiac-specific genes and play a crucial role in cardiogenesis.