Regulation of cyclin D2 gene expression by the Myc/Max/Mad network: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter

Myc oncoproteins promote cell cycle progression in part through the transcr iptional up-regulation of the cyclin D2 gene. We now show that Myc is bound to the cyclin D2 promoter in vivo. Binding of Myc induces cyclin D2 expres sion and histone acetylation at a single nucleosome in a MycBoxII/TRRAP-dep endent manner. Downregulation of cyclin D2 mRNA expression in differentiati ng HL60 cells is preceded by a switch of promoter occupancy from Myc/Max to Mad/Max complexes, loss of TRRAP binding, increased HDAC1 binding, and his tone deacetylation. Thus, recruitment of TRRAP and regulation of histone ac etylation are critical for transcriptional activation by Myc.