Date Published: December 24, 2009
Publisher: Public Library of Science
Author(s): Séverine Mazaud Guittot, Marie France Bouchard, Jean-Philippe Robert-Grenon, Claude Robert, Cynthia G. Goodyer, David W. Silversides, Robert S. Viger, Grzegorz Kudla. http://doi.org/10.1371/journal.pone.0008454
Abstract: 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.
Partial Text: 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). GATA proteins share a highly homologous zinc finger DNA binding domain which is also highly conserved from invertebrates to mammals . GATA family members display distinctive but overlapping expression patterns, both temporally and spatially. GATA1, 2, and 3 are primarily expressed in cells of the hematopoietic lineage (e.g., primitive erythroblasts, megakaryocytes, T cells, eosinophils), embryonic brain and liver, testis, and endothelial cells –. Conversely, GATA4, 5, and 6 are primarily detected in mesoderm- and endoderm-derived tissues such as the heart, lung, stomach, intestine, gonads, and blood vessels , , . 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 , , .
GATA4 is a member of the GATA family of transcriptional regulators that is required for the development and differentiation of numerous organs in the early embryo. This pivotal developmental role emphasizes the importance of understanding the molecular mechanisms that regulate expression of the GATA4 gene. Despite its critical role in organogenesis, our knowledge of GATA4 gene transcription remains surprisingly limited. Here, we report the identification of novel GATA4 transcripts that differ solely in their non-coding first exons. These alternative first exons are located several kilobases upstream of the classic GATA4 transcription initiation site suggesting that their expression is being driven from novel upstream promoters. The fact that some of these first exons are species-conserved also indicates that alternative promoter usage is likely an important regulatory mechanism for controlling the tissue- and cell-specific expression of the GATA4 gene in humans and other mammalian species.