Abstract 1571: TAZ Functions as a Coactivator of GATA Family Proteins, and Notch Signaling Represses GATA Activity through TAZ
The zinc finger transcription factors, GATA4 and GATA6, are important regulators of gene expression in cardiac and smooth muscle cell types. Here we show that the WW domain-containing cofactor, TAZ functions as a coactivator of GATA4 and GATA6. TAZ stimulates GATA4 and GATA6 activity on the ANF and BNP promoters in several cell lines. In contrast, a dominant-negative mutant of TAZ represses BNP and ANF promoter activity in cardiac myocytes. TAZ and GATA4 physically interact with each other thorough the N-terminal region of TAZ and activation domain of GATA4. Although TAZ does not bind to DNA, TAZ is recruited to the BNP promoter region through association with GATA4. TAZ does not have intrinsic HAT activity, but TAZ interacts with HAT proteins, p300 and PCAF, to stimulate GATA4 activity. HRT and HES family proteins, down stream targets of the Notch signaling pathway, interact with TAZ and inhibit GATA4 and GATA6 activity. HRT and HES family proteins also inhibit the activity of TBX5 and Runx2, which are activated by TAZ. These results suggest that HRT and HES family proteins can function as repressors of TAZ, and the Notch signaling pathway may regulate the activity of cardiac transcription factors including GATA family proteins by inhibiting their coactivator, TAZ.