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Research Article

Alternative Promoter and GATA5 Transcripts in Mouse

¹University of Chicago ²The University of Chicago ³University of Pennsylvania

Submitted 30 April 2009 ; revision received 27 August 2009 ; accepted in final form 17 September 2009

ABSTRACT

GATA5 is a member of the GATA zinc finger transcription factor family involved in tissue-specific transcriptional regulation during cell differentiation and embryogenesis. Previous reports indicate that null mutation of the zebrafish GATA5 gene results in embryonic lethality, while deletion of exon 1 from the mouse GATA5 gene causes only derangement of female urogenital development. Here, we have identified an alternate promoter within intron 1 of the mouse GATA5 gene that transcribes a 2.5 kb mRNA that lacks exon 1 entirely, but includes 82 bp from intron 1 and all of exons 2-6. The alternative promoter was active during transient transfection in cultured airway myocytes and bronchial epithelial cells, and drove reporter gene expression in gastric epithelial cells in transgenic mice. The 2.5 kb alternative transcript encodes an N-terminally truncated "short GATA5" comprising aa 226-404 with a single zinc finger, that retains ability to transactivate the ANF promoter (albeit less efficiently than full-length GATA5). Another new GATA5 transcript contains all of exons 1-5 and the 5' portion of exon 6, but lacks the terminal 1143 bp of the 3' UTR from exon 6. These findings extend current understanding of the tissue distribution of GATA5 expression and suggests that GATA5 expression and function are more complex than previously appreciated.

differentiation; airway; gut; epithelium