Department of Biochemistry, School of Medicine, Research Institute of Medical Science, Konkuk University, Seoul 05029, Korea.
Int J Mol Sci. 2020 Jun 1;21(11):3969. doi: 10.3390/ijms21113969.
Switch/sucrose non-fermentable (SWI/SNF)-related matrix-associated actin-dependent regulator of chromatin (SMARC) subfamily B member 1 (SMARCB1) is a core subunit of the switch/sucrose non-fermentable (SWI/SNF) complex, one of the adenosine triphosphate (ATP)-dependent chromatin remodeler complexes. The unique role of SMARCB1 has been reported in various cellular contexts. Here, we focused on the general role of the ubiquitous expression of SMARCB1 in a normal cell state. We selected ARPE19 (human primary retinal pigment epithelium) and IMR90 (from human fetal lung fibroblasts) cell lines as they have completely different contexts. Furthermore, although these cell lines have been immortalized, they are relatively close to normal human cells. The loss of SMARCB1 in ARPE19 and IMR90 cells reduced cell cycle progression via the upregulation of P21. Transcriptome analysis followed by SMARCB1 knockdown in both cell lines revealed that SMARCB1 was not only involved in cell maintenance but also conferred immunomodulation. Of note, SMARCB1 bound to interleukin (IL) 6 promoter in a steady state and dissociated in an active immune response state, suggesting that SMARCB1 was a direct repressor of IL6, which was further confirmed via loss- and gain-of-function studies. Taken together, we demonstrated that SMARCB1 is a critical gatekeeper molecule of the cell cycle and immune response.
SWI/SNF 相关基质相关肌动蛋白依赖性染色质调节因子（SMARC）亚家族 B 成员 1（SMARCB1）是开关/蔗糖非发酵（SWI/SNF）复合物的核心亚基之一，是一种三磷酸腺苷（ATP）依赖性染色质重塑复合物。SMARCB1 在各种细胞环境中的独特作用已有报道。在这里，我们专注于普遍表达的 SMARCB1 在正常细胞状态中的一般作用。我们选择 ARPE19（人原代视网膜色素上皮）和 IMR90（来自人胎儿肺成纤维细胞）细胞系，因为它们具有完全不同的背景。此外，尽管这些细胞系已经永生化，但它们与正常人类细胞相对接近。SMARCB1 在 ARPE19 和 IMR90 细胞中的缺失通过上调 P21 来减少细胞周期进程。在这两种细胞系中进行转录组分析并敲低 SMARCB1 后，发现 SMARCB1 不仅参与细胞维持，而且还具有免疫调节作用。值得注意的是，SMARCB1 在稳定状态下与白细胞介素（IL）6 启动子结合，并在活跃的免疫反应状态下解离，表明 SMARCB1 是 IL6 的直接抑制剂，这通过缺失和获得功能研究进一步得到证实。总之，我们证明了 SMARCB1 是细胞周期和免疫反应的关键守门员分子。
