SMARCB1 Acts as a Quiescent Gatekeeper for Cell Cycle and Immune Response in Human Cells

• Published in: International journal of molecular sciences Vol. 21; no. 11; p. 3969
• Main Authors: Choi, Sung Kyung, Kim, Myoung Jun, You, Jueng Soo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01.06.2020; MDPI
• Subjects: Actin; Adenosine triphosphate; Adenosine Triphosphate - metabolism; ATP; Biotechnology; Cell Cycle; Cell Line; Cell lines; Chromatin; Cytokines; Deoxyribonucleic acid; DNA; Epithelium; Fetuses; Fibroblasts; Fibroblasts - metabolism; Gene expression; Gene Expression Profiling; Gene Expression Regulation; Genetic engineering; Humans; Immune response; Immune system; Immunity; Immunomodulation; Interleukin 6; Interleukin-6 - metabolism; Investigations; Kinases; Proteins; Retinal pigment epithelium; Retinal Pigment Epithelium - metabolism; Senescence; SMARCB1; SMARCB1 Protein - physiology; Stem cells; Sucrose; SWI-SNF; Transcriptome; Tumor necrosis factor-TNF; interleukin 6; SMARCB1; cell cycle; immune response; SWI-SNF
• ISSN: 1422-0067; 1661-6596; 1422-0067
• 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.