SUMO-1 Modification Activated GATA4-dependent Cardiogenic Gene Activity*

Sumoylation, an important posttranslational modification process, is involved in regulating bioactivities of diverse proteins. GATA4, a cardiac-enriched dual zinc finger transcription factor, plays a critical role in regulating cardiac-specified genes. Here, we demonstrated that GATA4 is sumoylated by small ubiquitin-like modifier-1 (SUMO-1), which resulted in enhanced GATA4 transcriptional activity. We further revealed that lysine 366 of GATA4 constituted a major sumyolation site. Conversion of lysine 366 to arginine 366 resulted in reduced GATA4 nuclear occupation, suggesting that SUMO modification may also modulate GATA4 nuclear localization. In GATA4 sumoylation, PIAS1 served as an E3 ligase and positively modulated GATA4 transactivation via its RING finger domain. In the presence of SUMO-1 and/or PIAS1, GATA4 triggered the activation of cardiogenic genes in pluripotent 10T1/2 fibroblast. GATA4 was identified as a SUMO-1-targeted transcription factor and together with PIAS1 was shown to be a potent regulator of cardiac gene activity.

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