Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle (RNA-seq)

SETD1A catalyzes methylation of histone 3 lysine 4 (H3K4) and plays a critical role in development of multiple cancers. The abrrent expression of SETD1A relates to poor prognosis of gastric cancer (GC) patients. Here, we revealed that SETD1A is required for GC cell proliferation. Rescue experiment showed catalytic function is not necessary for GC cell growth and gene expression, whereas a novel non-catalytic FLOS domain is indispensable. The CRISPR screening targeting SETD1A targets identified that TAF6 acts as a downstream target of SETD1A which is essential for GC cell survival. Both SETD1A and TAF6 are required for G1/S cell cycle progression in GC cells. Non-catalytic component of SETD1A regulating expression of TAF6 through coactivating with E2F4s. These results demonstrate that non-canonical roles of SETD1A in GC cell, which supplys a potential therapeutic opportunity for GC. Overall design: To investigate SETD1A regulated genes in gastric cancer cells, we established SETD1A wt or knockout cell lines (AGS, SNU719 and MKN45). Then RNA-seq was performed in these cells.