Step-brothers in arms, SAGA and ATAC co-activator complexes, use different strategies.

Transcriptional co-activator complexes play essential roles in regulating gene transcription by integrating signals from transcription factors and chromatin. Among these, the SAGA (Spt-Ada-Gcn5 acetyltransferase) and ATAC (Ada Two-A Containing) complexes represent related histone acetyltransferase assemblies that contain both shared and specific subunits. SAGA and ATAC possess similar and divergent enzymatic activities that shape their contributions to transcriptional control. Here, we review emerging evidence that highlights differential interactions of transcriptional activators with SAGA or ATAC and their differential chromatin-reading capabilities through specific recognition of histone modifications. Distinct requirements for SAGA and for ATAC have been observed in gene regulation important for maintaining cellular homeostasis and for oncogenic transformation, indicating that dysregulation of these complexes can contribute to cancer progression. The development of small-molecule inhibitors targeting key components of SAGA and/or ATAC offers promising strategies to disrupt their recruitment and transcriptional activity in cancer cells. Our review dissects the unique and overlapping functions of SAGA and ATAC, which are crucial for understanding regulation by these complexes in order to exploit them as targets in precision oncology.