Bidirectional Crosstalk Between the SAGA Complex Deubiquitinase Module and the Molecular Circadian Clock

Abstract

The Spt-Ada-Gcn5-acetyltransferase (SAGA) complex is a highly conserved chromatin-modifying transcriptional coactivator that regulates gene expression through both transcriptional and post-translational mechanisms. In addition to histone acetyltransferase activity, SAGA harbors a deubiquitinase module (DUBm) that influences protein stability, localization, and function by removal of ubiquitin. Although SAGAs roles in transcription are well characterized, how its enzymatic modules are dynamically regulated to coordinate its divergent activities remains less known. Here, we identify a bidirectional relationship between the molecular circadian clock and the SAGA DUBm. Our results indicate that circadian rhythms influence DUBm activities and expression, while the DUBm in turn shapes the timing and stability of core clock proteins and transcripts, positioning the DUBm as an important mediator of the molecular circadian clock.