ATAC and SAGA histone acetyltransferase modules facilitate transcription factor binding to nucleosomes in an acetylation independent manner

Abstract

Transcription initiation involves the coordination of multiple events, starting with activators binding specific DNA target sequences, which recruits transcription co-activators to open chromatin and enable binding of general transcription factors and RNA polymerase II to promoters. Two key human transcriptional coactivator complexes, ATAC (ADA-Two-A-Containing) and SAGA (Spt-Ada-Gcn5-acetyltransferase), target genomic loci to increase promoter accessibility. To better understand the function of ATAC and SAGA histone acetyltransferase (HAT) complexes, we used in vitro biochemical and biophysical assays to characterize human ATAC and SAGA HAT module interactions with nucleosomes and how a transcription factor (TF) coordinates these interactions. We found that ATAC and SAGA HAT modules bind nucleosomes with high affinity, independent of post-translational modifications (PTMs) and TFs. ATAC and SAGA HAT modules directly interact with the VP16 activator domain and a TF containing this domain enhances HAT module acetylation activity. Surprisingly, ATAC and SAGA HAT modules increase TF binding to its DNA target site within the nucleosome by an order of magnitude independent of histone acetylation. Altogether, our results reveal synergistic coordination between HAT modules and a TF, where ATAC and SAGA HAT modules: (i) acetylate histones to open chromatin, and (ii) facilitate TF targeting within nucleosomes independently of their acetylation activity.