Moloney Murine Leukemia Virus (M-MLV) proviral DNA is transcriptionally silenced in embryonic cells by a large repressor complex tethered to the provirus by two sequence-specific DNA binding proteins, ZFP809 and YY1. A central component of the complex is Trim28, a scaffold protein that regulates many target genes involved in cell cycle progression, DNA damage responses, and viral gene expression. The silencing activity of Trim28, and its interactions with corepressors are often regulated by post-translational modifications such as sumoylation and phosphorylation. We defined the interaction domains of Trim28 and YY1, and investigated the role of sumoylation and phosphorylation of Trim28 in mediating M-MLV silencing. The RBCC domain of Trim28 was sufficient for interaction with YY1, and acidic region 1 and zinc fingers of YY1 were necessary and sufficient for its interaction with Trim28. Additionally, we found that residue K779 was critical for Trim28-mediated silencing of M-MLV in embryonic cells.

莫洛尼鼠白血病病毒 (M-MLV) 原病毒 DNA 在胚胎细胞中被一个大型阻遏复合物转录沉默，该复合体通过两种序列特异性 DNA 结合蛋白 ZFP809 和 YY1 与原病毒相连。该复合物的一个核心成分是 Trim28，这是一种支架蛋白，可调节参与细胞周期进程、DNA 损伤反应和病毒基因表达的许多靶基因。Trim28 的沉默活性及其与辅抑制因子的相互作用通常受翻译后修饰（如 sumoylation 和磷酸化）的调节。我们定义了 Trim28 和 YY1 的相互作用域，并研究了 Trim28 的 sumoylation 和磷酸化在介导 M-MLV 沉默中的作用。Trim28 的 RBCC 结构域足以与 YY1 相互作用，YY1 的酸性区域 1 和锌指是其与 Trim28 相互作用的必要条件。此外，我们发现残基 K779 对于 Trim28 介导的胚胎细胞 M-MLV 沉默至关重要。