RESULTS: In this study, we used MLV to explore the role of Smarcad1 in retroviral silencing in ESCs. We show that Smarcad1 is immediately recruited to the MLV provirus. Based on the repression dynamics of a GFP-reporter MLV, our findings suggest that Smarcad1 plays a critical role in the establishment and maintenance of MLV repression, as well as other Trim28-targeted genomic loci. Furthermore, Smarcad1 is important for stabilizing and strengthening Trim28 binding to the provirus over time, and its presence around the provirus is needed for proper deposition of H3.3 on the provirus. Surprisingly, the combined depletion of Smarcad1 and Trim28 results in enhanced MLV derepression, suggesting that these two proteins may also function independently to maintain repressive chromatin states.
CONCLUSIONS: Overall, the results of this study provide evidence for the crucial role of Smarcad1 in the silencing of retroviral elements in embryonic stem cells. Further research is needed to fully understand how Smarcad1 and Trim28 cooperate and their implications for gene expression and genomic stability.
结果:在这项研究中,我们使用MLV探讨Smarcad1在ESCs逆转录病毒沉默中的作用.我们表明Smarcad1立即被招募到MLV前病毒中。基于GFP-报道基因MLV的抑制动力学,我们的研究结果表明,Smarcad1在建立和维持MLV抑制中起关键作用,以及其他Trim28靶向基因组基因座。此外,Smarcad1对于随着时间的推移稳定和加强Trim28与前病毒的结合非常重要,H3.3在原病毒上的适当沉积需要它在原病毒周围的存在。令人惊讶的是,Smarcad1和Trim28的联合消耗导致增强的MLV抑制,这表明这两种蛋白质也可能独立发挥作用,以维持抑制性染色质状态。
结论:总体而言,这项研究的结果为Smarcad1在胚胎干细胞中逆转录病毒元件沉默中的关键作用提供了证据。需要进一步的研究来充分了解Smarcad1和Trim28如何合作以及它们对基因表达和基因组稳定性的影响。