Gene Regulation of GATA-4 transcription factor and pathology

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1.Transcription start sites of GATA-4 gene were not significantly different between rat heart, stomach and testis. In the cardiac myocyte differentiation model (mouse P19.CL6 cells), GATA-4 gene was activated, immediately after induction by DMSO. An E-box and two GC-boxes were important for transcription of GATA-4 gene. However, the -124 bp region with these three boxes was not enough for the induced-expression of reporter gene that was constructed by ligating this 124 bp sequence to the 5'-side of GFP gene. Further upstream -125 〜 -1312 bp region together was required for the induced expression.2.The cAMP-dependent proteolysis occurred in CHO-K1 cells. The potential phosphorylation site by A-kinase and the PEST sequence on the GATA-6 were not required for the proteolysis, and rather other cellular protein(s) could be a target for A-kinase. Thus it would be of interest to identify novel cellular factor(s) functioning in A-kinase pathway.3.Two translational isoforms (L- and S-types) were formed from a single mRNA, since additional translational initiation codon was present in frame in the further 5'-upstream region of GATA-6 mRNA being not recognized previously. L-type GATA-6 had extended 146 amino acid residues. The 16-residue region in the L-type specific sequence was required for the extended structure of L-type GATA-6. Furthermore, transcriptional activation potency of L-type GATA-6 was higher. Roles of protein factor(s) interacting with the L-type specific region would be interesting from view points of complex formation and transcriptional regulation.4.Both L- and S-type GATA-6 were expressed in human cancer cell lines. The growth regulation of such cancer cells through GATA-6 would be next study, since we have now known many molecular properties of GATA-6 in the present research project.