SUMOylation, covalent conjugation of small ubiquitin-related modifier (SUMO), has been emerging as a critical posttranslational modification of developmental transcription factors, as well as key regulators in the adult heart. Identifying the SUMOylated targets within cardiac transcription factors will facilitate to unravel the roles of SUMOylation in heart development and disease. Here, we show that Gata6, an essential cardiac transcription factor, can be modified by SUMO in vivo. Mutation of potential SUMOylation sites reveals that a lysine residue at amino acid position 12 of Gata6 serves as the major attachment site for SUMO. Pias1, as an E3 SUMO ligase, preferentially enhances the conjugation of SUMO1 to Gata6 through its RING finger domain. Functional analyses with SUMOylation-deficient mutant indicate that SUMOylation does not affect the subcellular localization but instead represses Gata6 transcriptional activity. Our data suggest that posttranslational modification of Gata6 by SUMO conjugation provides a novel mechanism to regulate Gata6 activity.

中文翻译：

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SUMO对心脏转录因子Gata6的修饰。

SUMOylation是小泛素相关修饰物（SUMO）的共价缀合，已成为发育转录因子以及成年心脏中关键调节剂的关键翻译后修饰。在心脏转录因子中鉴定SUMO化的靶标将有助于阐明SUMO化在心脏发育和疾病中的作用。在这里，我们显示了必需的心脏转录因子Gata6在体内可以被SUMO修饰。潜在SUMOylation位点的突变表明，Gata6氨基酸位置12处的赖氨酸残基是SUMO的主要附着位点。Pias1作为E3 SUMO连接酶，优先通过其RING指域增强SUMO1与Gata6的结合。SUMOylation缺陷突变体的功能分析表明SUMOylation不会影响亚细胞定位，而是抑制Gata6转录活性。我们的数据表明，SUMO缀合对Gata6进行翻译后修饰，提供了一种调节Gata6活性的新机制。