Regulation of CtISWI Activity by AutoN and HSS Domain

Chromatin remodeler imitation switch (ISWI) plays an important role in regulating chromatin structure through sliding and spacing nucleosomes. Despite the enormous progress in regulatory elements and mechanisms of the activity of ISWI in recent years, there are still some unclear structures and mechanisms in different species. Here, we studied the ATPase activity and nucleosome binding affinity of Chaetomium thermophilum ISWI (hereafter referred to as CtISWIWT) and several mutants, further proving the importance of these mutated residues in the inhibition of AutoN. We also analyzed the effects of dsDNA and ssDNA on ATPase activity of CtISWI, suggesting the potential interaction between HSS and ATPase domain. Notably, we provided a predicted structural model based on the sequence of CtISWIWT, proposing a two-step activating mechanism of conformation change and activity regulation. Taken together, our findings elucidate a different model of ISWI self-maintenance and action, providing a new mechanism of regulation supporting chromatin remodeling.