SIRT7-dependent deacetylation of CDK9 activates RNA polymerase II transcription

Blank, Maximilian F.; Chen, Sifan; Poetz, Fabian; Schnölzer, Martina; Voit, Renate; Grummt, Ingrid

Among the proteins detected in the SIRT7 proteome was RPB2, suggesting that SIRT7 interacts with Pol II. The C-terminal domain (CTD) of RPB1 is modified by reversible phosphorylation, acetylation and methylation, all of which are implicated in Pol II recruitment and transcription (30, 39, 40) . Notably, both the proteomic data and the results of co-immunoprecipitation experiments revealed that SIRT7 is also associated with the positive transcription elongation factor P-TEFb comprising CDK9 and cyclin T1. Moreover, SIRT7 was found to be associated with 7SK RNA (13) and with the 7SK-associated protein HEXIM1. Together with the observation that SIRT7 interacts with elongating Pol II and co-localizes with Pol II phosphorylated at CTD-Ser2 at SIRT7 target genes, these results suggested that reversible acetylation may regulate CDK9 kinase activity and transcription elongation. CDK9 is acetylated at two lysine residues, K44 and K48 (31) (32) (33) . GCN5-mediated in vivo acetylation preferentially targets K48 which is essential for ATP binding and CDK9 activity.