RNA-seq profiling of human A549 cells with knockdown of chromatin remodeling factor BAZ1A

Cellular senescence is a well-known cancer prevention mechanism, inducing cancer cells to senescence can enhance cancer immunotherapy. However, how cellular senescence is regulated is not fully understood. Dynamic chromatin changes have been discovered during cellular senescence, while the causality remains elusive. We discovered that BAZ1A, a gene coding the accessory subunit of ATP-dependent chromatin remodeling complex, showed decreased expression in multiple cellular senescence models. Knockdown (KD) of BAZ1A in both normal and cancer cells induced series of senescence-associated phenotypes. BAZ1A-KD induced differentially expressed genes were enriched in senescence-related pathways such as p53 signaling pathway and TGF-β signaling pathway in lung cancer cells. Mechanistically, BAZ1A bound to the promoter region of transcription factor SMAD3 and repressed its expression. BAZ1A-KD caused the upregulated expression of SMAD3, which in turn activated the transcription of p21 coding gene CDKN1A and resulted in senescence-associated phenotypes. Furthermore, knockdown of SMARCA5, the other subunit of ATP-dependent chromatin remodeling complex, led to reduced BAZ1A and cellular senescence, suggesting SMARCA5 was one regulator of BAZ1A in regulating cellular senescence.