Abstract
BackgroundGATA4 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 FindingsUsing 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/SignificanceTaken 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.
Highlights
The GATA proteins are a small family of transcriptional regulators composed of 6 members that bind the common consensus sequence motif (A/T)GATA(A/G)
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
To verify that GATA4 is no exception to the 59 untranslated exon rule, and to gain additional insights into the transcriptional mechanisms that regulate GATA4 gene expression, we analyzed the 59 ends of GATA4 transcripts by 59 RACE (Figure 1A and B)
Summary
The GATA proteins are a small family of transcriptional regulators composed of 6 members that bind the common consensus sequence motif (A/T)GATA(A/G). GATA4, 5, and 6 are primarily detected in mesoderm- and endoderm-derived tissues such as the heart, lung, stomach, intestine, gonads, and blood vessels [3,5,6]. In agreement with these expression patterns, numerous GATA knockout models in mice as well as the in vitro identification of GATA target genes have revealed the crucial role of GATA factors for cellular differentiation during vertebrate organogenesis [2,5,6]. 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 59 region of the mouse, rat, and human GATA4 genes
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