Competitive antagonism of KAT7 crotonylation against acetylation affects procentriole formation and colorectal tumorigenesis

Abstract

Accurate procentriole formation is critical for centriole duplication. However, the holistic transcriptional regulatory mechanisms underlying this process remain elusive. Here, we show that KAT7 crotonylation, facilitated by the crotonyltransferase hMOF, competes against its acetylation regulated by the deacetylase HDAC2 at the K432 residue upon DNA damage stimulation. This competition diminishes its histone acetyltransferase activity, leading to the inhibition of procentriole formation in colorectal cancer cells. Mechanistically, the reduction of KAT7 histone acetyltransferase activity by the antagonistic effect of KAT7 crotonylation against its acetylation decreases the gene expression associated with procentriole formation by modulating the enrichment of H3K14ac at their promoters and plays an important role in colorectal tumorigenesis. Furthermore, KAT7 crotonylation and acetylation are associated with the prognosis in colorectal cancer patients. Collectively, our findings uncover a previously unidentified role of KAT7 in the regulation of procentriole formation and colorectal tumorigenesis via competitive antagonism of its crotonylation against acetylation.