PARP1 modulates METTL3 promoter chromatin accessibility and associated LPAR5 RNA m⁶A methylation to control cancer cell radiosensitivity.

ABSTRACT: Chromatin remodeling and N⁶-methyladenosine (m⁶A) modification are two critical layers in controlling gene expression and DNA damage signaling in most eukaryotic bioprocesses. Here, we report that poly(ADP-ribose) polymerase 1 (PARP1) controls the chromatin accessibility of METTL3 to regulate its transcription and subsequent m⁶A methylation of poly(A)⁺ RNA in response to DNA damage induced by radiation. The transcription factors nuclear factor I-C (NFIC) and TATA binding protein (TBP) are dependent on PARP1 to access the METTL3 promoter to activate METTL3 transcription. Upon irradiation or PARP1 inhibitor treatment, PARP1 disassociated from METTL3 promoter chromatin, which resulted in attenuated accessibility of NFIC and TBP and, consequently, su

SUBMITTER: Sun X 

PROVIDER: S-EPMC10492194 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature