Early growth response 1 promotes RNA polymerase I-directed transcription and cancer growth by activating RRN3 expression

Early growth response 1 (EGR1) was identified as a positive regulator in Pol II- and Pol Ⅲ-directed transcription. Whether EGR1 modulates Pol Ⅰ-directed transcription remains unknown. Here, we report that EGR1 is present in the nucleoli of several cancer cell lines. EGR1 positively regulates the synthesis of Pol Ⅰ products and the proliferation of HeLa, HePG2, and AGS cells both in vitro and in vivo. EGR1 silencing increased R-loop formation and lncRNA PAPAS expression, which inversely correlated with Pol Ⅰ product levels. Mechanistically, EGR1 enhances the recruitment of Pol I transcription machinery factors to the rDNA promoter through interactions with these factors. The EGR1 DNA-binding domain mediates the interaction between EGR1 and Pol I machinery components. EGR1 activates RRN3 gene transcription by binding to the RRN3 gene promoter. Thus, EGR1 promotes Pol Ⅰ-directed transcription and cancer cell growth by both interacting with Pol I machinery factors and controlling RRN3 expression.