Inhibition of FoxO1 acetylation by INHAT subunit SET/TAF-Iß induces p21 transcription.

Post-translational modification of forkhead family transcription factor, FoxO1, is an important regulatory mode for its diverse activities. FoxO1 is acetylated by HAT coactivators and its transcriptional activity is decreased via reduced DNA binding affinity. Here, we report that SET/TAF-Iß inhibited p300-mediated FoxO1 acetylation in an INHAT domain-dependent manner. SET/TAF-Iß interacted with FoxO1 and activated transcription of FoxO1 target gene, p21. Moreover, SET/TAF-Iß inhibited acetylation of FoxO1 and increased p21 transcription induced by oxidative stress. Our results suggest that SET/TAF-Iß inhibits FoxO1 acetylation and activates its transcriptional activity toward p21.