Conserved Usage of Alternative 5′ Untranslated Exons of the GATA4 Gene

BACKGROUND: GATA4 is an essential transcription factor required for the development and function of multiple organs. Despite this important role, our knowledge of how the GATA4 gene is regulated remains limited. To better understand this regulation, we characterized the 5′ region of the mouse, rat, and human GATA4 genes. METHODOLOGY/PRINCIPAL FINDINGS: Using 5′ RACE, we identified novel transcription start sites in all three species. GATA4 is expressed as multiple transcripts with varying 5′ ends encoded by alternative untranslated first exons. Two of these non-coding first exons are conserved between species: exon 1a located 3.5 kb upstream of the GATA4 ATG site in exon 2, and a second first exon (exon 1b) located 28 kb further upstream. Expression of both mRNA variants was found in all GATA4-expressing organs but with a preference for the exon 1a–containing transcript. The exception was the testis where exon 1a– and 1b–containing transcripts were similarly expressed. In some tissues such as the intestine, alternative transcript expression appears to be regionally regulated. Polysome analysis suggests that both mRNA variants contribute to GATA4 protein synthesis. CONCLUSIONS/SIGNIFICANCE: Taken together, our results indicate that the GATA4 gene closely resembles the other GATA family members in terms of gene structure where alternative first exon usage appears to be an important mechanism for regulating its tissue- and cell-specific expression.