An unexpected role for Dicer as a reader of the unacetylated DNA binding domain of p53 in transcriptional regulation.

ABSTRACT: Here, we identified Dicer as a major cellular factor that recognizes the DNA binding domain (DBD) of p53 in a manner dependent on its acetylation status. Upon binding the unacetylated DBD, Dicer is recruited to the promoters of p53 target genes, where it represses p53-mediated transcriptional activation. Conversely, knockdown or knockout of endogenous Dicer leads to up-regulation of p53-mediated transcriptional activation without increasing its protein levels. Moreover, Dicer-mediated repression is independent of its intrinsic endoribonuclease activity; instead, Dicer directly represses transcription by recruiting the SUV39H1 histone methyltransferase. However, upon DNA damage, Dicer-mediated repression is abrogated by stress-induced acetylation at the DBD of p53. Notably, the inability of

SUBMITTER: Yang X 

PROVIDER: S-EPMC8550248 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature